Platelet-Rich Plasma in Young and Elderly Humans Exhibits a Different Proteomic Profile.

As people age, their ability to resist injury and repair damage decreases significantly. Platelet-rich plasma (PRP) has demonstrated diverse therapeutic effects on tissue repair. However, the inconsistency of patient outcomes poses a challenge to the practical application of PRP in clinical practice. Furthermore, a comprehensive understanding of the specific impact of aging on PRP requires a systematic investigation. We derived PRP from 6 young volunteers and 6 elderly volunteers, respectively. Subsequently, 95% of high-abundance proteins were removed, followed by mass spectrometry analysis. Data are available via ProteomeXchange with the identifier PXD050061. We detected a total of 739 proteins and selected 311 proteins that showed significant differences, including 76 upregulated proteins in the young group and 235 upregulated proteins in the elderly group. Functional annotation and enrichment analysis unveiled upregulation of proteins associated with cell apoptosis, angiogenesis, and complement and coagulation cascades in the elderly. Conversely, IGF1 was found to be upregulated in the young group, potentially serving as the central source of enhanced cell proliferation ability. Our investigation not only provides insights into standardizing PRP preparation but also offers novel strategies for augmenting the functionality of aging cells or tissues.

Cardiac-specific deletion of heat shock protein 60 induces mitochondrial stress and disrupts heart development in mice.

Congenital heart diseases are the most common birth defects around the world. Emerging evidence suggests that mitochondrial homeostasis is required for normal heart development. In mitochondria, a series of molecular chaperones including heat shock protein 60 (HSP60) are engaged in assisting the import and folding of mitochondrial proteins. However, it remains largely obscure whether and how these mitochondrial chaperones regulate cardiac development. Here, we generated a cardiac-specific Hspd1 deletion mouse model by αMHC-Cre and investigated the role of HSP60 in cardiac development. We observed that deletion of HSP60 in embryonic cardiomyocytes resulted in abnormal heart development and embryonic lethality, characterized by reduced cardiac cell proliferation and thinner ventricular walls, highlighting an essential role of cardiac HSP60 in embryonic heart development and survival. Our results also demonstrated that HSP60 deficiency caused significant downregulation of mitochondrial ETC subunits and induced mitochondrial stress. Analysis of gene expression revealed that P21 that negatively regulates cell proliferation is significantly upregulated in HSP60 knockout hearts. Moreover, HSP60 deficiency induced activation of eIF2α-ATF4 pathway, further indicating the underlying mitochondrial stress in cardiomyocytes after HSP60 deletion. Taken together, our study demonstrated that regular function of mitochondrial chaperones is pivotal for maintaining normal mitochondrial homeostasis and embryonic heart development.

NLSI: An innovative method to locate epidemic sources on the SEIR propagation model.

Epidemics pose a significant threat to societal development. Accurately and swiftly identifying the source of an outbreak is crucial for controlling the spread of an epidemic and minimizing its impact. However, existing research on locating epidemic sources often overlooks the fact that epidemics have an incubation period and fails to consider social behaviors like self-isolation during the spread of the epidemic. In this study, we first take into account isolation behavior and introduce the Susceptible-Exposed-Infected-Recovered (SEIR) propagation model to simulate the spread of epidemics. As the epidemic reaches a certain threshold, government agencies or hospitals will report the IDs of some infected individuals and the time when symptoms first appear. The reported individuals, along with their first and second-order neighbors, are then isolated. Using the moment of symptom onset reported by the isolated individuals, we propose a node-level classification method and subsequently develop the node-level-based source identification (NLSI) algorithm. Extensive experiments demonstrate that the NLSI algorithm is capable of solving the source identification problem for single and multiple sources under the SEIR propagation model. We find that the source identification accuracy is higher when the infection rate is lower, and a sparse network structure is beneficial to source localization. Furthermore, we discover that the length of the isolation period has little impact on source localization, while the length of the incubation period significantly affects the accuracy of source localization. This research offers a novel approach for identifying the origin of the epidemic associated with our defined SEIR model.

Cardiac lipidomic profiles in mice undergo changes from fetus to adult.

AIMS: Lipids are essential cellular components with many important biological functions. Disturbed lipid biosynthesis and metabolism has been shown to cause cardiac developmental abnormality and cardiovascular diseases. In this study, we aimed to investigate the composition and the molecular profiles of lipids in mammalian hearts between embryonic and adult stages and uncover the underlying links between lipid and cardiac development and maturation. MATERIALS AND METHODS: We collected mouse hearts at the embryonic day 11.5 (E11.5), E15.5, and the age of 2 months, 4 months and 10 months, and performed lipidomic analysis to determine the changes of the composition, molecular species, and relative abundance of cardiac lipids between embryonic and adult stages. Additionally, we also performed the electronic microscopy and RNA sequencing in both embryonic and adult mouse hearts. KEY FINDINGS: The relative abundances of certain phospholipids and sphingolipids including cardiolipin, phosphatidylglycerol, phosphatidylethanolamine, and ceramide, are different between embryonic and adult hearts. Such lipidomic changes are accompanied with increased densities of mitochondrial membranes and elevated expression of genes related to mitochondrial formation in adult mouse hearts. We also analyzed individual molecular species of phospholipids and sphingolipids, and revealed that the composition and distribution of lipid molecular species in hearts also change with development. SIGNIFICANCE: Our study provides not only a lipidomic view of mammalian hearts when developing from the embryonic to the adult stage, but also a potential pool of lipid indicators for cardiac cell development and maturation.

IP3R-mediated Ca2+ signaling controls B cell proliferation through metabolic reprogramming.

Emerging evidence shows that metabolic regulation may be a critical mechanism in B cell activation and function. As targets of several most widely used immunosuppressants, Ca2+ signaling and calcineurin may play an important role in regulating B cell metabolism. Here, we demonstrate that IP3R-mediated Ca2+ signaling and calcineurin regulate B cell proliferation and survival by activating metabolic reprogramming in response to B cell receptor (BCR) stimulation. Both IP3R-triple-knockout (IP3R-TKO) and calcineurin inhibition dramatically suppress the metabolic switch in oxidative phosphorylation and glycolysis of stimulated B cells through regulation of glucose uptake, glycolytic enzyme expression, and mitochondrial remodeling, leading to impaired cell-cycle entry and survival. In addition, IP3R-Ca2+ acts as a master regulator of the calcineurin-MEF2C-Myc pathway in driving B cell metabolic adaptations. As genetic defects of IP3Rs were recently identified as a new class of inborn errors of immunity, these results have important implications for understanding the pathogenesis of such diseases.

High Accuracy Human Activity Recognition Based on Sparse Locality Preserving Projections.

Human activity recognition(HAR) from the temporal streams of sensory data has been applied to many fields, such as healthcare services, intelligent environments and cyber security. However, the classification accuracy of most existed methods is not enough in some applications, especially for healthcare services. In order to improving accuracy, it is necessary to develop a novel method which will take full account of the intrinsic sequential characteristics for time-series sensory data. Moreover, each human activity may has correlated feature relationship at different levels. Therefore, in this paper, we propose a three-stage continuous hidden Markov model (TSCHMM) approach to recognize human activities. The proposed method contains coarse, fine and accurate classification. The feature reduction is an important step in classification processing. In this paper, sparse locality preserving projections (SpLPP) is exploited to determine the optimal feature subsets for accurate classification of the stationary-activity data. It can extract more discriminative activities features from the sensor data compared with locality preserving projections. Furthermore, all of the gyro-based features are used for accurate classification of the moving data. Compared with other methods, our method uses significantly less number of features, and the over-all accuracy has been obviously improved.

Sensitivity and selectivity determination of BPA in real water samples using PAMAM dendrimer and CoTe quantum dots modified glassy carbon electrode.

Bisphenol A (BPA) is an environmental pollutant to disrupt endocrine system or cause cancer, thus the detection of BPA is very important. Herein, an amperometric sensor was fabricated based on immobilized CoTe quantum dots (CoTe QDs) and PAMAM dendrimer (PAMAM) onto glassy carbon electrode (GCE) surface. The cyclic voltammogram of BPA on the sensor exhibited a well-defined anodic peak at 0.490V in 0.1M pH 8.0 PBS. The determination conditions were optimized and the kinetic parameters were calculated. The linear range was 1.3 x 10(-8) to 9.89 x 10(-6)M with the correlation coefficient of 0.9999. The limit of detection was estimated to be 1 x 10(-9)M. The current reached the steady-state current within about 5s. Furthermore, the fabricated sensor was successfully applied to determine BPA in real water samples.

A nitrite biosensor based on the immobilization of cytochrome c on multi-walled carbon nanotubes-PAMAM-chitosan nanocomposite modified glass carbon electrode.

A novel nitrite biosensor was successfully prepared via immobilizing Cytochrome c (Cyt c) onto the multi-walled carbon nanotubes-poly(amidoamine) (PAMAM)-chitosan (MWNT-PAMAM-Chit) nanocomposite modified glass carbon electrode (GCE). Ultraviolet and visible (UV-vis) absorption spectrum, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to examine the native conformation and bioactivity of the immobilized Cyt c, and the electrochemical properties of the modified electrodes, respectively. The results indicate that the immobilized Cyt c retained its native characters, and the MWNT-PAMAM-Chit nanocomposite is a good platform for the immobilization of Cyt c as well as an excellent promoter for the electron transfer between Cyt c and electrode. The high reactive Cyt c pi-cation, which can oxidize NO(2)(-) into NO(3)(-) in the solution, is generated at higher potential (>0.7 V) based on the further oxidation of Cyt c. The nitrite biosensor showed a fast response to nitrite (about 5 s) in two concentration intervals, one was from 0.1 to 29 microM, and the other from 29 to 254 microM. The low detection limit of 0.01 microM was obtained.