Receptor-interacting protein kinase-3 （RIP3 or RIPK3） is an essential part of the cellular machinery that executes ＂programmed＂ or ＂regulated＂ necrosis. Here we show that programmed necrosis is ...activated in response to many chemotherapeutic agents and contributes to chemotherapy-induced cell death. However, we show that RIP3 expres- sion is often silenced in cancer cells due to genomic methylation near its transcriptional start site, thus RIP3-depen- dent activation of MLKL and downstream programmed necrosis during chemotherapeutic death is largely repressed. Nevertheless, treatment with hypomethylating agents restores RIP3 expression, and thereby promotes sensitivity to chemotherapeutics in a RIP3-dependent manner. RIP3 expression is reduced in tumors compared to normal tissue in 85% of breast cancer patients, suggesting that RIP3 deficiency is positively selected during tumor growth/develop- ment. Since hypomethylating agents are reasonably well-tolerated in patients, we propose that RIP3-deficient cancer patients may benefit from receiving hypomethylating agents to induce RIP3 expression prior to treatment with con- ventional chemotherapeutics.
Electrochemically converting nitrate, a widespread water pollutant, back to valuable ammonia is a green and delocalized route for ammonia synthesis, and can be an appealing and supplementary ...alternative to the Haber-Bosch process. However, as there are other nitrate reduction pathways present, selectively guiding the reaction pathway towards ammonia is currently challenged by the lack of efficient catalysts. Here we report a selective and active nitrate reduction to ammonia on Fe single atom catalyst, with a maximal ammonia Faradaic efficiency of ~ 75% and a yield rate of up to ~ 20,000 μg h
mg
(0.46 mmol h
cm
). Our Fe single atom catalyst can effectively prevent the N-N coupling step required for N
due to the lack of neighboring metal sites, promoting ammonia product selectivity. Density functional theory calculations reveal the reaction mechanisms and the potential limiting steps for nitrate reduction on atomically dispersed Fe sites.
Abstract
Oxygen reduction reaction towards hydrogen peroxide (H
2
O
2
) provides a green alternative route for H
2
O
2
production, but it lacks efficient catalysts to achieve high selectivity and ...activity simultaneously under industrial-relevant production rates. Here we report a boron-doped carbon (B-C) catalyst which can overcome this activity-selectivity dilemma. Compared to the state-of-the-art oxidized carbon catalyst, B-C catalyst presents enhanced activity (saving more than 210 mV overpotential) under industrial-relevant currents (up to 300 mA cm
−2
) while maintaining high H
2
O
2
selectivity (85–90%). Density-functional theory calculations reveal that the boron dopant site is responsible for high H
2
O
2
activity and selectivity due to low thermodynamic and kinetic barriers. Employed in our porous solid electrolyte reactor, the B-C catalyst demonstrates a direct and continuous generation of pure H
2
O
2
solutions with high selectivity (up to 95%) and high H
2
O
2
partial currents (up to ~400 mA cm
−2
), illustrating the catalyst’s great potential for practical applications in the future.
We describe the epidemiology of a coronavirus disease (COVID-19) outbreak in a call center in South Korea. We obtained information on demographic characteristics by using standardized epidemiologic ...investigation forms. We performed descriptive analyses and reported the results as frequencies and proportions for categoric variables. Of 1,143 persons who were tested for COVID-19, a total of 97 (8.5%, 95% CI 7.0%-10.3%) had confirmed cases. Of these, 94 were working in an 11th-floor call center with 216 employees, translating to an attack rate of 43.5% (95% CI 36.9%-50.4%). The household secondary attack rate among symptomatic case-patients was 16.2% (95% CI 11.6%- 22.0%). Of the 97 persons with confirmed COVID-19, only 4 (1.9%) remained asymptomatic within 14 days of quarantine, and none of their household contacts acquired secondary infections. Extensive contact tracing, testing all contacts, and early quarantine blocked further transmission and might be effective for containing rapid outbreaks in crowded work settings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
P38 mitogen-activated protein kinase (MAPK) is a crucial target for chronic inflammatory diseases. Alzheimer's disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary ...tangles in the brain, as well as neurodegeneration, and there is no known cure. Recent studies on the underlying biology of AD in cellular and animal models have indicated that p38 MAPK is capable of orchestrating diverse events related to AD, such as tau phosphorylation, neurotoxicity, neuroinflammation and synaptic dysfunction. Thus, the inhibition of p38 MAPK is considered a promising strategy for the treatment of AD. In this review, we summarize recent advances in the targeting of p38 MAPK as a potential strategy for the treatment of AD and envision possibilities of p38 MAPK inhibitors as a fundamental therapeutics for AD.
Although archaea, Gram-negative bacteria, and mammalian cells constitutively secrete membrane vesicles (MVs) as a mechanism for cell-free intercellular communication, this cellular process has been ...overlooked in Gram-positive bacteria. Here, we found for the first time that Gram-positive bacteria naturally produce MVs into the extracellular milieu. Further characterizations showed that the density and size of Staphylococcus aureus-derived MVs are both similar to those of Gram-negative bacteria. With a proteomics approach, we identified with high confidence a total of 90 protein components of S. aureus-derived MVs. In the group of identified proteins, the highly enriched extracellular proteins suggested that a specific sorting mechanism for vesicular proteins exists. We also identified proteins that facilitate the transfer of proteins to other bacteria, as well to eliminate competing organisms, antibiotic resistance, pathological functions in systemic infections, and MV biogenesis. Taken together, these observations suggest that the secretion of MVs is an evolutionally conserved, universal process that occurs from simple organisms to complex multicellular organisms. This information will help us not only to elucidate the biogenesis and functions of MVs, but also to develop therapeutic tools for vaccines, diagnosis, and antibiotics effective against pathogenic strains of Gram-positive bacteria.
Virtual Reality (VR) is increasingly used in health-related fields and interventions using VR have the potential to be powerful tools in patient management. The aim of this study was to synthesize ...the effects of VR interventions for people with mild cognitive impairment (MCI) or dementia.
Electronic databases were searched to identify studies that used an experimental design to investigate VR intervention outcomes for patients with MCI or dementia. Studies were excluded if the intervention did not focus on VR, if relevant quantitative outcomes were not reported, or if the intended study purpose was assessment or diagnosis. Data were extracted and analyzed from studies that met criteria. To synthesize the intervention effect sizes (ES), we used random effects models to accommodate heterogeneity in the main effect and sub-group analyses. To identify the potential reason for heterogeneity and compare ES according to the moderator variables, subgroup analyses were conducted based on study characteristics and intervention outcomes.
Data from eleven studies that met eligibility criteria were analyzed. VR intervention delivered to participants with MCI or dementia produced small to medium effects (ES = 0.29, CI = 0.16, 0.42). The ES for studies using semi-immersive technology (ES = 0.37, CI = 0.25, 0.49) was greater than the studies using full-immersive VR (ES = 0.03, CI = -0.14, 0.21). The results showed small-to-medium effects for VR interventions affecting key outcome variables such as cognition (ES = 0.42, CI = 0.24, 0.60) and physical fitness (ES = 0.41, CI = 0.16, 0.65).
VR interventions, particularly of the semi-immersive type, are useful for people with MCI or dementia. These results should contribute to the establishment of practical guidelines for VR interventions for patients with cognitive decline.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transition-metal single-atom catalysts present extraordinary activity per metal atomic site, but suffer from low metal-atom densities (typically less than 5 wt% or 1 at.%), which limits their overall ...catalytic performance. Here we report a general method for the synthesis of single-atom catalysts with high transition-metal-atom loadings of up to 40 wt% or 3.8 at.%, representing several-fold improvements compared to benchmarks in the literature. Graphene quantum dots, later interweaved into a carbon matrix, were used as a support, providing numerous anchoring sites and thus facilitating the generation of high densities of transition-metal atoms with sufficient spacing between the metal atoms to avoid aggregation. A significant increase in activity in electrochemical CO2 reduction (used as a representative reaction) was demonstrated on a Ni single-atom catalyst with increased Ni loading.Transition-metal single-atom catalysts display excellent activity per metal atom site, but suffer from low metal atom densities (typically less than 5 wt% or 1 at.%), which limits their overall catalytic performance. Now, the use of a graphene-quantum-dot primary support, later interweaved into a carbon matrix, has enabled the synthesis of single-atom catalysts with high transition-metal atom loadings of up to 40 wt% or 3.84 at.%.
The ongoing surge in demand for high‐performance energy storage systems inspires the relentless pursuit of advanced materials and structures. Components of energy storage systems are generally based ...on inorganic/metal compounds, carbonaceous substances, and petroleum‐derived hydrocarbon chemicals. These traditional materials, however, may have difficulties fulfilling the ever‐increasing requirements of energy storage systems. Recently, nanocellulose has garnered considerable attention as an exceptional 1D element due to its natural abundance, environmental friendliness, recyclability, structural uniqueness, facile modification, and dimensional stability. Recent advances and future outlooks of nanocellulose as a green material for energy storage systems are described, with a focus on its application in supercapacitors, lithium‐ion batteries (LIBs), and post‐LIBs. Nanocellulose is typically classified as cellulose nanofibril (CNF), cellulose nanocrystal (CNC), and bacterial cellulose (BC). The unusual 1D structure and chemical functionalities of nanocellulose bring unprecedented benefits to the fabrication and performance of energy storage materials and systems, which lie far beyond those achievable with conventional synthetic materials. It is believed that this progress report can stimulate research interests in nanocellulose as a promising material, eventually widening material horizons for the development of next‐generation energy storage systems, that will lead us closer to so‐called Battery‐of‐Things (BoT) era.
Recent advances and future outlook of nanocellulose for potential use in energy storage systems are described as a green material opportunity. The unusual 1D structure and chemical functionalities of nanocellulose bring unprecedented benefits in the fabrication and properties of energy storage materials and systems, which lie far beyond those achievable with traditional synthetic materials.
A
bstract
In this paper, we explore the physics of electromagnetically and gravitationally coupled massive higher spin states from the on-shell point of view. Starting with the three-point amplitude, ...we focus on the simplest amplitude characterized by matching to minimal coupling in the UV. In the IR, for charged states this leads to
g
= 2 for arbitrary spin, and the leading deformation corresponds to the anomalous magnetic dipole moment. We proceed to construct the (gravitational) Compton amplitude for generic spins via consistent factorization. We find that in gravitation couplings, the leading deformation leads to inconsistent factorization. This implies that for systems with Gauge
2
= Gravity relations, such as perturbative string theory, all charged states must have
g
= 2. It is then natural to ask for generic spin, what is the theory that yields such minimal coupling. By matching to the one body effective action, we verify that for large spins the answer is Kerr black holes. This identification is then an on-shell avatar of the no- hair theorem. Finally using this identification as well as the newly constructed Compton amplitudes, we proceed to compute the spin-dependent pieces for the classical potential at 2PM order up to degree four in spin operator of either black holes.
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