MDM2-p53 mediate a miR-181c-3p/LIF axis to regulate low dose-rate radiation-induced DNA damage in human B lymphocytes.

PURPOSE: Prolonged exposure to low dose-rate radiation (LDRR) is of growing concern to public health. Recent evidences indicates that LDRR causes deleterious health effects and is closely related to miRNAs. The aim of our study is to investigate the relationship between miRNAs and DNA damage caused by LDRR. MATERIALS AND METHODS: In this study, we irradiated C57BL/6J mice with 12.5µGy/h dose of γ ray emitted from uranium ore for 8 h a day for 120 days at a total dose of 12 mGy, and identified differentially expressed miRNAs from the mice long-term exposed to LDRR through isolating serum RNAs, constructing small RNA library, Illumina sequencing. To further investigate the role of differential miRNA under LDRR，we first built DNA damage model in Immortal B cells irradiated with 12.5µGy/h dose of γ ray for 28 days at a total dose of 9.4 mGy. Then, we chose the highly conserved miR-181c-3p among 12 miRNA and its mechanism in alleviating DNA damage induced by LDRR was studied by transfection, quantitative PCR, luciferase assay, and Western blot. RESULTS AND CONCLUSIONS: We have found that 12 differentially expressed miRNAs including miR-181c-3p in serum isolated from irradiated mice. Analysis of GO and KEGG indicated that target genes of theses 12 miRNA enriched in pathways related to membrane, protein binding and cancer. Long-term exposure to LDRR induced upregulation of gamma-H2A histone family member X (γ-H2AX) expression, a classical biomarker for DNA damage in B cells. miR-181c-3p inhibited Leukemia inhibitory factor (LIF) expression via combining its 3'UTR. LIF, MDM2, p53, and p-p53-s6 were upregulated after exposure to LDRR. In irradiated B cells, Transfection of miR-181c-3p reduced γ-H2AX expression and suppressed LIF and MDM2 protein levels, whereas p-p53-s6 expression was increased. As expected, the effect of LIF inhibition on irradiated B cells was similar to miR-181c-3p overexpression. Our results suggest that LDRR alters miRNA expression and induces DNA damage. Furthermore, miR-181c-3p can alleviate LDRR-induced DNA damage via the LIF/MDM2/p-p53-s6 pathway in human B lymphocytes. This could provide the basis for prevention and treatment of LDRR injury.

The role of stromal cells in epithelial-mesenchymal plasticity and its therapeutic potential.

The epithelial-mesenchymal transition (EMT) is a critical tumor invasion and metastasis process. EMT enables tumor cells to migrate, detach from their original location, enter the circulation, circulate within it, and eventually exit from blood arteries to colonize in foreign sites, leading to the development of overt metastases, ultimately resulting in death. EMT is intimately tied to stromal cells around the tumor and is controlled by a range of cytokines secreted by stromal cells. This review summarizes recent research on stromal cell-mediated EMT in tumor invasion and metastasis. We also discuss the effects of various stromal cells on EMT induction and focus on the molecular mechanisms by which several significant stromal cells convert from foes to friends of cancer cells to fuel EMT processes via their secretions in the tumor microenvironment (TME). As a result, a better knowledge of the role of stromal cells in cancer cells' EMT may pave the path to cancer eradication.

Analysis of the spatial differentiation and driving force of arable land abandonment and non-grain in the hilly mountainous areas of Gannan.

Food security has a bearing on national development and people's livelihoods and is an important guarantee of social stability for national development. The problems of arable land abandonment and non-grain are becoming more and more serious, and national food security is difficult to guarantee, which will seriously hinder the forward development of China's society and economy. Taking Ruijin City of Jiangxi Province as an example, this study calculated the abandonment level and non-grain level of arable land in Ruijin City respectively from two aspects, and explored the spatial differentiation law of farmland abandonment and non-grain level in the hilly and mountainous areas of southern Jiangxi Province by using spatial autocorrelation and cold and hot spot analysis methods, and the causes of arable land abandonment and non-grain spatial differentiation in the hilly mountainous areas of Gannan were revealed by the methods of Geodetector factor detection and interaction detection. Conclusions of the study: (1) Ruijin City, the abandoned area was 1216.73 hm2, the abandonment rate of each village ranged from 0.01 % to 50.62 %, and the comprehensive abandonment rate was 4.90 %; the area of non-grain was 2937.27 hm2, and the rate of non-grain of each village ranged from 0.01 % to 100.00 %, and the comprehensive non-grain rate was 11.83 %. The area of non-grain was 2937.27 hm2, and the rate of non-grain in each village ranged from 0.01 % to 100.00 %, and the comprehensive rate of non-grain was 11.83 %. (2) The phenomenon of abandonment of arable land and non-grain in Gannan hilly and mountainous areas has a certain clustering and driving effect in space. Globally, the phenomena of arable land abandonment and non-grain in Ruijin City are positively correlated, with the global Moran's I of arable land abandonment rate being 0.05, and the global Moran's I of arable land non-grain being 0.73. (3) Whether or not arable land in the hilly mountainous areas of Gannan is abandoned is affected by the combination of socioeconomics, natural resources, farming conditions, and economic location, with elevation, the degree of arable land contiguity, and population density being the dominant factors. The interaction of elevation, degree of concentration and contiguity, field regularity, and per capita arable land area increased the spatial variability of arable land abandonment in the hilly mountainous areas of Gannan. Whether the phenomenon of non-grain occurs or not is affected by socio-economic conditions, farming conditions and economic location, of which the proportion of paddy fields, land transfer price, arable land area, and urban-rural gradient are the dominant factors. The proportion of paddy land, the price of land transfer, the area of arable land, and the urban-rural gradient interact with each other, and the tendency of arable land to be planted with non-grain crops is more serious.

The Improvement and Related Mechanism of Microecologics on the Sports Performance and Post-Exercise Recovery of Athletes: A Narrative Review.

The diversity and functionality of gut microbiota may play a crucial role in the function of human motor-related systems. In addition to traditional nutritional supplements, there is growing interest in microecologics due to their potential to enhance sports performance and facilitate post-exercise recovery by modulating the gut microecological environment. However, there is a lack of relevant reviews on this topic. This review provides a comprehensive overview of studies investigating the effects of various types of microecologics, such as probiotics, prebiotics, synbiotics, and postbiotics, on enhancing sports performance and facilitating post-exercise recovery by regulating energy metabolism, mitigating oxidative-stress-induced damage, modulating immune responses, and attenuating bone loss. Although further investigations are warranted to elucidate the underlying mechanisms through which microecologics exert their effects. In summary, this study aims to provide scientific evidence for the future development of microecologics in athletics.

Dietary Patterns, Gut Microbiota and Sports Performance in Athletes: A Narrative Review.

The intestinal tract of humans harbors a dynamic and complex bacterial community known as the gut microbiota, which plays a crucial role in regulating functions such as metabolism and immunity in the human body. Numerous studies conducted in recent decades have also highlighted the significant potential of the gut microbiota in promoting human health. It is widely recognized that training and nutrition strategies are pivotal factors that allow athletes to achieve optimal performance. Consequently, there has been an increasing focus on whether training and dietary patterns influence sports performance through their impact on the gut microbiota. In this review, we aim to present the concept and primary functions of the gut microbiota, explore the relationship between exercise and the gut microbiota, and specifically examine the popular dietary patterns associated with athletes' sports performance while considering their interaction with the gut microbiota. Finally, we discuss the potential mechanisms by which dietary patterns affect sports performance from a nutritional perspective, aiming to elucidate the intricate interplay among dietary patterns, the gut microbiota, and sports performance. We have found that the precise application of specific dietary patterns (ketogenic diet, plant-based diet, high-protein diet, Mediterranean diet, and high intake of carbohydrate) can improve vascular function and reduce the risk of illness in health promotion, etc., as well as promoting recovery and controlling weight with regard to improving sports performance, etc. In conclusion, although it can be inferred that certain aspects of an athlete's ability may benefit from specific dietary patterns mediated by the gut microbiota to some extent, further high-quality clinical studies are warranted to substantiate these claims and elucidate the underlying mechanisms.

Scalable high-throughput microfluidic separation of magnetic microparticles.

Surface-engineered magnetic microparticles are used in chemical and biomedical engineering due to their ease of synthesis, high surface-to-volume ratio, selective binding, and magnetic separation. To separate them from fluid suspensions, existing methods rely on the magnetic force introduced by the local magnetic field gradient. However, this strategy has poor scalability because the magnetic field gradient decreases rapidly as one moves away from the magnets. Here, we present a scalable high-throughput magnetic separation strategy using a rotating permanent magnet and two-dimensional arrays of micromagnets. Under a dynamic magnetic field, nickel micromagnets allow the surrounding magnetic microparticles to self-assemble into large clusters and effectively propel themselves through the flow. The collective speed of the microparticle swarm reaches about two orders of magnitude higher than the gradient-based separation method over a wide range of operating frequencies and distances from a rotating magnet.

A sulfur-modified pore-blocking method to enhance the electrocatalytic stability of carbon-supported platinum nanoparticles.

Currently, the durability of electrode materials remains a big obstacle to the widespread adoption of proton exchange membrane fuel cells (PEMFCs). Herein thiourea and sodium dodecyl benzene sulfonate (SDS) were employed as sulfur source and carbon source to modify the pristine carbon black (Ketjen black EC300 J). A highly durable carbon supported Pt nanosized catalyst with higher platinum utilization for oxygen reduction reaction (ORR) in PEMFCs was produced by doping elemental sulfur into carbon supports and decreasing the carbon pore sizes and volume through a successive impregnation technique. The catalyst exhibits an initial activity of 0.167 A mgPt -1 at 0.90 V and demonstrates minimal activity loss after acceleration stress test (30,000 cycles of AST). The half-wave potential loss for representative sample (Pt/S-C-3) is only 14 mV with only 21.8 % ECSA decrease, 27.5 % MA loss and 5.9 % SA loss. A sintering test at various temperature shows a minor average size increase for sulfur-doped carbon (S-C) supported one (from 2.09 to 2.52 nm). In single-cell test, the MEA sample employing the platinum catalyst on modified carbon as cathode exhibited almost negligible performance loss after 30,000 cycles of AST.

Electroacupuncture regulates histone acetylation of Bcl-2 and Caspase-3 genes to improve ischemic stroke injury.

Background: Imbalances between Bcl-2 and caspase-3 are significant evidence of apoptosis, which is considered an influential factor in rapidly occurring neuronal cell death and the decline of neurological function after stroke. Studies have shown that acupuncture can reduce poststroke brain cell damage via either an increase in Bcl-2 or a reduction in caspase-3 exposure. The current study aimed to investigate whether acupuncture could modulate Bcl-2 and caspase-3 expression through histone acetylation modifications, which could potentially serve as a neuroprotective mechanism. Methods: This study used TTC staining, Nissl staining, Clark neurological system score, and Evans Blue (EB) extravasation to evaluate neurological damage following stroke. The expression of Bcl-2/caspase-3 mRNA was detected by real-time fluorescence quantification of PCR (real-time PCR), whereas the protein expression levels of Bcl-2, Bax, caspase-3, and cleaved caspase-3 were assessed using western blotting. TUNEL staining of the ischemic cortical neurons determined apoptosis in the ischemic cortex. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities, along with the protein performance of AceH3, H3K9ace, and H3K27ace, were detected to evaluate the degree of histone acetylation. The acetylation enrichment levels of H3K9 and K3K27 in the Bcl-2/caspase-3 gene were assessed using Chromatin Immunoprecipitation (ChIP) assay. Results: Our data demonstrated that electroacupuncture (EA) exerts a significant neuroprotective effect in middle cerebral artery occlusion (MCAO) rats, as evidenced by a reduction in infarct volume, neuronal damage, Blood-Brain Barrier (BBB) disruption, and decreased apoptosis of ischemic cortical neurons. EA treatment can promote the mRNA and protein expression of the Bcl-2 gene in the ischemic brain while reducing the mRNA and protein expression levels of caspase-3 and effectively decreasing the protein expression levels of Bax and cleaved caspase-3. More importantly, EA treatment enhanced the level of histone acetylation, including Ace-H3, H3K9ace, and H3K27ace, significantly enhanced the occupancy of H3K9ace/H3K27ace at the Bcl-2 promoter, and reduced the enrichment of H3K9ace and H3K27ace at the caspase-3 promoter. However, the Histone Acetyltransferase inhibitor (HATi) treatment reversed these effects. Conclusions: Our data demonstrated that EA mediated the expression levels of Bcl-2 and caspase-3 in MCAO rats by regulating the occupancy of acetylated H3K9/H3K27 at the promoters of these two genes, thus exerting a cerebral protective effect in ischemic reperfusion (I/R) injury.

Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

An ingestible, battery-free, tissue-adhering robotic interface for non-invasive and chronic electrostimulation of the gut.

Ingestible electronics have the capacity to transform our ability to effectively diagnose and potentially treat a broad set of conditions. Current applications could be significantly enhanced by addressing poor electrode-tissue contact, lack of navigation, short dwell time, and limited battery life. Here we report the development of an ingestible, battery-free, and tissue-adhering robotic interface (IngRI) for non-invasive and chronic electrostimulation of the gut, which addresses challenges associated with contact, navigation, retention, and powering (C-N-R-P) faced by existing ingestibles. We show that near-field inductive coupling operating near 13.56 MHz was sufficient to power and modulate the IngRI to deliver therapeutically relevant electrostimulation, which can be further enhanced by a bio-inspired, hydrogel-enabled adhesive interface. In swine models, we demonstrated the electrical interaction of IngRI with the gastric mucosa by recording conductive signaling from the subcutaneous space. We further observed changes in plasma ghrelin levels, the "hunger hormone," while IngRI was activated in vivo, demonstrating its clinical potential in regulating appetite and treating other endocrine conditions. The results of this study suggest that concepts inspired by soft and wireless skin-interfacing electronic devices can be applied to ingestible electronics with potential clinical applications for evaluating and treating gastrointestinal conditions.

Cross-sensitivity analysis of land use transition and ecological service values in rare earth mining areas in southern China.

Exploring the cross-sensitivity between land use transformation and ecological service values in rare earth mining areas is of great significance for the development of ecological protection and restoration in rare earth mining areas. To study the impact of land use changes on ecosystem service functions in rare earth mining areas, firstly, the land use change trends in the study area from 2009 to 2019 were analyzed using the land transfer matrix; then the distribution of ecosystem service values and the flow direction of ecosystem service values in the study area were measured based on the ecosystem service value equivalents; a spatial autocorrelation analysis was done on the ecosystem service values to explore their spatial distribution patterns; and finally, the cross-sensitivity coefficient was used to quantitatively assess the extent and direction of the impact of land use change on ecosystem service values. The results show that the land use types in the study area are mainly forest land and farmland, with woodland accounting for the highest proportion of the study area. The ESV changes in the study area are consistent with the trend of land use transformation, with the overall increase and decrease being comparable, and the decrease in ESV is mainly concentrated in the areas with a large increase in mining land and construction land; during the study period, the study area was significantly reduced with low-low cluster areas and the ecological environment was improved; from 2009 to 2014, the ecological sensitivity coefficient is more variable, and is more sensitive to the net conversion between water and desert, from 2014 to 2019, the ecological sensitivity coefficient is less variable, and the most sensitive is the net conversion between cultivated land and water. The study area should be reasonably developed for rare earth resources and the ecological environment around the mining area should be reasonably protected to build an ecological security pattern.