Inflammatory biomarkers of frailty: A review Zhang, Liying; Zeng, Xiaofeng; He, Fuqian ...
Experimental gerontology,
August 2023, 2023-Aug, 2023-08-00, 20230801, 2023-08-01, Volume:
179
Journal Article
Peer reviewed
Open access
Frailty is a common geriatric syndrome characterized by increased vulnerability and is associated with adverse clinical events such as falls, hospitalization, and death. Early diagnosis and early ...intervention can delay or reverse frailty and ensure the healthy aging of older individuals. At present, there are no gold standard biomarkers for the diagnosis of frailty, which mainly relies on the scale to assess frailty, and the scale has shortcomings such as lagging assessment, subjectivity, and poor consistency. Frailty biomarkers help in early diagnosis and intervention in frailty. The purpose of this review is to summarize the existing inflammatory markers of frailty and focus on novel inflammatory biomarkers of frailty that can be used to help identify frailty early and explore potential intervention targets.
•Inflammation is closely related to frailty, and the study of frailty and inflammation is in full swing.•The latest research findings, including inflammaging, and potential biomarkers of frailty were summarized.•Exploring the specific biomarkers of frailty is helpful to assess frailty and ensure the healthy aging of older adults.
Abstract
Compression of hydrogen-rich hydrides has been proposed as an alternative way to attain the atomic metallic hydrogen state or high-temperature superconductors. However, it remains a ...challenge to get access to these states by synthesizing novel polyhydrides with unusually high hydrogen-to-metal ratios. Here we synthesize a series of cerium (Ce) polyhydrides by a direct reaction of Ce and H
2
at high pressures. We discover that cerium polyhydride CeH
9
, formed above 100 GPa, presents a three-dimensional hydrogen network composed of clathrate H
29
cages. The electron localization function together with band structure calculations elucidate the weak electron localization between H-H atoms and confirm its metallic character. By means of Ce atom doping, metallic hydrogen structure can be realized via the existence of CeH
9
. Particularly, Ce atoms play a positive role to stabilize the sublattice of hydrogen cages similar to the recently discovered near-room-temperature lanthanum hydride superconductors.
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•The concentrations of various N forms in dry season was higher than that in wet season.•Gate construction significantly changed the N transport processes.•Sewage/manure has become ...the major N source in waterbody.•Urban N sources input has surpassed that of agricultural sources.•Sediment N release became the second-largest N source in waterbody under the hydrodynamic disturbances.
Revealing nitrogen source and transport mechanisms are essential to achieving optimal nitrogen management in urban estuaries and gate-controlled rivers. However, in plains river networks, gate and/or dam construction make the nitrogen sources difficult to trace. In this study, seasonal water samples from typical urban estuaries and gate-controlled rivers in northern Taihu Lake were analyzed using statistical analysis and stable isotope analysis in R (SIAR). The results show that the concentrations of various nitrogen forms showed obvious spatial–temporal distribution characteristics by multiple sources. Specifically, the nitrogen concentration was lower during the wet season than the dry season (T = 6.02, p < 0.01). Gate construction had a dual effect on the water environment, because it changed both the nitrogen transport processes and the nitrogen enrichment risk between the river side and lake side. The δ18O-NO3- and δ15N-NO3- values were sensitive to anthropogenic activity intensity and urbanization process, showing the following order of δ15N-NO3- values: Countryside > Suburbs > Downtown, and Construction Land > Forest-grassland > Farmland. While, a contrary trend was observed among the variations in δ18O-NO3- values. According to the SIAR model, sewage/manure, fertilizer, and sediment nitrogen (sediment N) were the main nitrate sources, accounting for 42.68%, 23.79%, and 23.71%, respectively. The proportion of urban nitrogen discharge has surpassed that of agricultural sources, becoming the largest nitrogen source in the waterbody. Under the coupling of meteorological conditions and estuary shape, the endogenous nitrogen released from sediment became the second largest contributor in some estuaries. These findings suggest that it is necessary to strengthen the control of urban exogenous nitrogen input and sediment nitrogen endogenous release to enable future estuarine nitrogen management and habitat restoration.
In recent years, it has been found that miRNA has a very close relationship with cardiovascular system diseases. Heart disease is accompanied by a change of the miRNA expression spectrum. Changing ...the expression of miRNA in or out of cells can cause heart diseases such as myocardial infarction, hypertrophy or arrhythmia. Mitogen-activated protein kinases (MAPKs) are important transmitters of cell surface signals to the nucleus. The family influences the biological responses of cells (e.g., proliferation, differentiation, transformation and apoptosis) by affecting the transcription and regulation of genes in animal cells. Based on the above background, the purpose of this study was to study the effect of the mir-1-mediated AMPK pathway on cardiomyocyte apoptosis in hypertensive rats. The expression level of miRNA-1 in cultured rat H9c2 cardiomyocytes was detected by real-time PCR to determine the success of the transfection. MTT method was used to detect the cell viability. Flow cytometry was used to detect the cell apoptosis, and real-time PCR and Western blot were used to detect the mRNA and protein expression of bcl-2. The results were compared with those of H9c2 cells (blank control group) and miRNA negative control fragments (negative control group). As an important kinase regulating energy homeostasis, AMPK is one of the central regulators of metabolism in eukaryotic cells and organisms, responsible for regulating cellular capacity input and output and maintaining the smooth functioning of cellular physiological activities. At the same time, AMPK is a key protein involved in a variety of signaling pathways. The results showed that the apoptosis rate of myocardial cells in the miRNA-1 group decreased (0.710 ± 0.009661)% vs (1.066667 ± 0.02603)% compared with that in the spontaneous hypertension control group (P < 0.001). The transfected miRNA-1mimics can up-regulate the expression of miRNA-1 in cells, inhibit the proliferation of cardiomyocytes and promote apoptosis.
This study is performed to explore the role of P2X4 in intracerebral hemorrhage (ICH) and the association between P2X4 and the NLRP1/Caspase-1 pathway. The mouse ICH model was established via ...collagenase injection into the right basal ganglia. P2X4 expression in brain tissues was knocked down via intracerebroventricular injection with adeno-associated virus (AAV) harboring shRNA against shP2X4. The gene expression of P2X4 and protein levels related to NLRP1 inflammasome were detected using qRT-PCR and Western blot analysis, respectively. Muramyl dipeptide (an activator of NLRP1) was used to activate NLRP1 in brain tissues. ICH induced high expression of P2X4 in mouse brain tissues. The knockdown of P2X4 alleviated short- and long-term neurological deficits of ICH mice, as well as inhibited the tissue expression and serum levels of pro-inflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-1β. Additionally, the expressions of NLRP1, ASC, and pro-Caspase-1 were down-regulated upon P2X4 silencing. Moreover, neurological impairment and the expression and secretion of cytokines after P2X4 silencing were aggravated by the additional administration of MDP. P2X4 knockdown represses neuroinflammation in brain tissues after ICH. Mechanistically, P2X4 inhibition exerts a neuroprotective effect in ICH by blocking the NLRP1/Caspase-1 pathway.
Ternary hydrides are regarded as an important platform for exploring high-temperature superconductivity at relatively low pressures. Here, we successfully synthesized the hcp-(La,Ce)H
at 113 GPa with ...the initial La/Ce ratio close to 3:1. The high-temperature superconductivity was strikingly observed at 176 K and 100 GPa with the extrapolated upper critical field H
(0) reaching 235 T. We also studied the binary La-H system for comparison, which exhibited a T
of 103 K at 78 GPa. The T
and H
(0) of the La-Ce-H are respectively enhanced by over 80 K and 100 T with respect to the binary La-H and Ce-H components. The experimental results and theoretical calculations indicate that the formation of the solid solution contributes not only to enhanced stability but also to superior superconducting properties. These results show how better superconductors can be engineered in the new hydrides by large addition of alloy-forming elements.
Over 3.8 billion years of evolution has enabled many microbial species a versatile metabolism. However, limited by experimental methods, some unique metabolism remains unknown or unclear. A major ...obstacle is to attribute the incorporation of certain nutrients into a noncultivable species out of a complex microbial community. Such difficulty could be solved if we are able to directly observe substrate uptake at the single-cell level. Nanoscale secondary ion mass spectrometry (NanoSIMS) is a powerful tool for revealing element distribution in nanometer-scale resolution in the fields such as material sciences, geosciences and astronomy. In this review, we focus on another applicability of NanoSIMS in microbiology. In such fields, physiological properties and metabolic activities of microorganisms can be revealed with a single-cell scale resolution by NanoSIMS solely or in combination with other techniques. This review will highlight the features of NanoSIMS in analyzing the metabolic activities of carbon, nitrogen, metal irons by mixed-culture assemblies. Some values of NanoSIMS in environmental microbiology are expected to be discussed via this review.
•Thermal conductivity(TC) of 3C-SiC was studied by (non-)/Equilibrium MD.•Effect of temperature and cascade collision on conductivity was explored.•Results of Tersoff/zbl and MEAM interatomic ...potential were illustrated.•Multiple-phase simulation was used and 4 kinds of point defects was counted.•Cascade collision caused by a higher-energy atom can induce lower TC of 3C-SiC.
The cubic silicon carbide 3C-SiC, the significant nuclear material used to manufacture the nuclear fuel in High Temperature Gas-cooled Reactor (HTGR), operates under a high temperature and neutron flux condition. The effect of temperature and irradiation on thermal conductivity of 3C-SiC were investigated with the molecular dynamics method. The equilibrium and non-equilibrium methods were utilized to calculate the thermal conductivity of 3C-SiC and the results of tersoff/zbl and MEAM interatomic potential were compared. Exponential decay of thermal conductivity with increasing temperature was illustrated. The irradiation effect was simulated with a high-energy Si atom and subsequent cascade collision, a multiple-phase simulation procedure was employed and the number of four kinds of point defects was counted. Finally, a relatively smaller simulation cell was used to analyze the impact of the incident atom with various velocities on the thermal conductivity of 3C-SiC. The computed results showed the cascade collision, caused by a higher-energy atom, would induce the lower thermal conductivity of 3C-SiC.
Proteins of the bromodomain and extra-terminal (BET) domain family are epigenetic readers that bind acetylated histones through their bromodomains to regulate gene transcription. Dual-bromodomain BET ...inhibitors (DbBi) that bind with similar affinities to the first (BD1) and second (BD2) bromodomains of BRD2, BRD3, BRD4 and BRDt have displayed modest clinical activity in monotherapy cancer trials. A reduced number of thrombocytes in the blood (thrombocytopenia) as well as symptoms of gastrointestinal toxicity are dose-limiting adverse events for some types of DbBi
. Given that similar haematological and gastrointestinal defects were observed after genetic silencing of Brd4 in mice
, the platelet and gastrointestinal toxicities may represent on-target activities associated with BET inhibition. The two individual bromodomains in BET family proteins may have distinct functions
and different cellular phenotypes after pharmacological inhibition of one or both bromodomains have been reported
, suggesting that selectively targeting one of the bromodomains may result in a different efficacy and tolerability profile compared with DbBi. Available compounds that are selective to individual domains lack sufficient potency and the pharmacokinetics properties that are required for in vivo efficacy and tolerability assessment
. Here we carried out a medicinal chemistry campaign that led to the discovery of ABBV-744, a highly potent and selective inhibitor of the BD2 domain of BET family proteins with drug-like properties. In contrast to the broad range of cell growth inhibition induced by DbBi, the antiproliferative activity of ABBV-744 was largely, but not exclusively, restricted to cell lines of acute myeloid leukaemia and prostate cancer that expressed the full-length androgen receptor (AR). ABBV-744 retained robust activity in prostate cancer xenografts, and showed fewer platelet and gastrointestinal toxicities than the DbBi ABBV-075
. Analyses of RNA expression and chromatin immunoprecipitation followed by sequencing revealed that ABBV-744 displaced BRD4 from AR-containing super-enhancers and inhibited AR-dependent transcription, with less impact on global transcription compared with ABBV-075. These results underscore the potential value of selectively targeting the BD2 domain of BET family proteins for cancer therapy.
A hydroxyl-functionalized ligand was designed for the construction of metal–organic framework (MOF) materials with the aggregation-induced emission (AIE) feature, in which the fluorescence can be ...deliberately tailored: quenching the fluorescence to an “off” state by the decoration with heterocyclic auxiliary ligand 4,4′-bypyridine (Bpy) in the framework as a quenching agent and triggering the enhanced fluorescence to an “on” state by removal of Bpy through the metal competitive coordination substitution strategy. Our study shows that the occurrence of exciton migration between the AIE linker and conjugated auxiliary ligand Bpy causes fluorescence quenching. Time-dependent density functional theory was employed to understand the photoinduced electron transfer process and explain the origins of fluorescence quenching. Using this strategy, the prepared MOF material can perform as a fluorescence “off–on” probe for highly sensitive detection of Al3+ in aqueous media. The hydroxyl group plays a crucial role in sensing as it can selectively chelate Al3+, which is directly related to the dissociation of nonfluorescent MOF and consequent activation of the AIE process.
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