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1.
Sci Rep ; 14(1): 12812, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834714

ABSTRACT

The importance of fuel mixing for the progress of the scramjet engine is indisputable. The present article shows the importance of the non-equal multi-injector system for effective fuel distribution and flame holding inside the combustion segment of a scramjet engine. The supersonic air and fuel jet flow in the non-equal nozzle arrangement is simulated via computational fluid dynamic technique. Two injector types of circular and rectangular nozzle have been analyzed to attain flow characteristics of hydrogen jets at supersonic cross flow. Mach contour is also analyzed for these jet arrangements to show the interface of the jet in the non-equal jet arrangement. Besides, addition of internal air jet is also simulated and evaluated in this research. Our investigation shows that the diffusion height of the fuel jet is higher when a rectangular non-equal nozzle is applied. The circular nozzle is more active in the spreading of the fuel in the combustor and the use of an internal air jet effectively increases fuel in a combustor of the scramjet.

2.
Phytomedicine ; 130: 155668, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38776739

ABSTRACT

BACKGROUND: Baoyuan decoction (BYD) has been widely utilized as a traditional prescription for the treatment of various conditions such as coronary heart disease, aplastic anemia, and chronic renal failure. However, its potential efficacy in improving atherosclerosis has not yet been investigated. PURPOSE: Our research aimed to assess the potential of BYD as an inhibitor of atherosclerosis and uncover the underlying mechanism by which it acts on foam cell formation. STUDY DESIGN AND METHODS: High-fat diet-induced ApoE-/- mice were employed to explore the effect of BYD on atherosclerosis. The differential metabolites in feces were identified and analyzed by LC-Qtrap-MS. In addition, we utilized pharmacological inhibition of BYD on foam cell formation induced by oxLDL in THP-1 cells to elucidate the underlying mechanisms specifically in macrophages. RESULTS: The atherosclerotic plaque burden in the aortic sinus of ApoE-/- mice was notably reduced with BYD treatment, despite no significant alterations in plasma lipids. Metabolomic analysis revealed that BYD suppressed the increased levels of peroxidized fatty acids, specifically 9/13-hydroxyoctadecadienoic acid (9/13-HODE), in the feces of mice. As a prominent peroxidized fatty acid found in oxLDL, we confirmed that 9/13-HODE induced the overexpression of CD36 in THP-1 macrophages by upregulating PPARγ. In subsequent experiments, the decreased levels of CD36 triggered by oxLDL were observed after BYD treatment. This decrease occurred through the regulation of the Src/MMK4/JNK pathway, resulting in the suppression of lipid deposition in THP-1 macrophages. CONCLUSIONS: These results illustrate that BYD exhibits potential anti-atherosclerotic effects by inhibiting CD36 expression to prevent foam cell formation.

3.
Psychol Med ; : 1-12, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563297

ABSTRACT

BACKGROUND: Despite extensive research into the neural basis of autism spectrum disorder (ASD), the presence of substantial biological and clinical heterogeneity among diagnosed individuals remains a major barrier. Commonly used case‒control designs assume homogeneity among subjects, which limits their ability to identify biological heterogeneity, while normative modeling pinpoints deviations from typical functional network development at individual level. METHODS: Using a world-wide multi-site database known as Autism Brain Imaging Data Exchange, we analyzed individuals with ASD and typically developed (TD) controls (total n = 1218) aged 5-40 years, generating individualized whole-brain network functional connectivity (FC) maps of age-related atypicality in ASD. We then used local polynomial regression to estimate a networkwise normative model of development and explored correlations between ASD symptoms and brain networks. RESULTS: We identified a subset exhibiting highly atypical individual-level FC, exceeding 2 standard deviation from the normative value. We also identified clinically relevant networks (mainly default mode network) at cohort level, since the outlier rates decreased with age in TD participants, but increased in those with autism. Moreover, deviations were linked to severity of repetitive behaviors and social communication symptoms. CONCLUSIONS: Individuals with ASD exhibit distinct, highly individualized trajectories of brain functional network development. In addition, distinct developmental trajectories were observed among ASD and TD individuals, suggesting that it may be challenging to identify true differences in network characteristics by comparing young children with ASD to their TD peers. This study enhances understanding of the biological heterogeneity of the disorder and can inform precision medicine.

4.
Geriatr Orthop Surg Rehabil ; 15: 21514593241250165, 2024.
Article in English | MEDLINE | ID: mdl-38681064

ABSTRACT

Objective: Preoperative frailty and surgical waiting times are associated with the occurrence of adverse outcomes in patients with hip fractures. Specifically, we aimed to investigate the influence of frailty status and surgical timing on the risk of serious adverse events during hospitalization. Methods: This study utilized an observational single cohort design and included patients aged ≥60 years with a primary diagnosis of hip fracture. Frailty was assessed using the chart-derived frailty index (CFI), which was calculated based on demographic and routine laboratory variables. The primary outcome of interest was the occurrence of in-hospital serious adverse events. A multivariate logistic regression model was utilized to examine the risk factors influencing outcomes. Results: The study included 427 participants, with a mean age of 80.28 ± 8.13 years and 64.2% of whom were female. Patients with high CFI have more comorbidities (P < .001), lower surgical rates (P = .002), and delayed surgical times (P = .033). A total of 239 patients (56.0%) experienced serious adverse events. The high CFI group had a significantly higher occurrence of serious adverse events compared to the low CFI group (73.4% vs 48.5%, P < .001). After adjusting for surgical timing and covariates, the multivariate logistic regression analysis revealed that high frailty significantly increased the risk for serious adverse events (OR = 2.47, 95% CI 1.398-4.412), infection (OR = 1.99, 95% CI 1.146-3.446), acute heart failure (OR = 3.37, 95% CI 1.607-7.045). However, the timing of surgery did not demonstrate any association with these outcomes. In addition, after adjusting for surgical factors, high CFI remains an independent risk factor for these complications. Conclusions: Frailty serves as a reliable predictor of the probability of encountering severe adverse events while hospitalized for elderly individuals with hip fractures. This method has the potential to pinpoint particular modifiable factors that necessitate intervention, whereas the impact of surgical timing remains uncertain and necessitates additional research.

5.
Inorg Chem ; 63(17): 7631-7639, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38625102

ABSTRACT

Two novel MoO42--templated luminescent silver alkynyl nanoclusters with 20-nuclearity ([(MoO42-)@Ag20(C≡CtBu)8(Ph2PO2)7(tfa)2]·(tfa-) (1)) and 18-nuclearity ([(MoO42-)@Ag18(C≡CtBu)8(Ph2PO2)7]·(OH) (2)) (tfa = trifluoroacetate) were synthesized with the green light maximum emissions at 507 and 516 nm, respectively. The nanoclusters were investigated and characterized by single-crystal X-ray crystallography, electrospray ionization mass spectrum (ESI-MS), X-ray photoelectron spectroscopy, thermogravimetry (TG), photoluminescence (PL), ultraviolet-visible (UV-vis) spectroscopy, and density functional theory calculations (DFT). The two nanoclusters differ in their structure by a supplementary [Ag2(tfa)2] organometallic surface motif, which significantly participates in the frontier molecular orbitals of 1, resulting in similar bonding patterns but different optical properties between the two clusters. Indeed, both nanoclusters show strong temperature-dependent photoluminescence properties, which make them potential candidates in the fields of optical devices for further applications.

6.
Analyst ; 149(10): 2877-2886, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38567989

ABSTRACT

Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is expressed ubiquitously in cancer cells and can metabolize exogenous substances. Studies show higher UGT1A1 levels in pancreatic cancer cells than normal cells. Therefore, we need a method to monitor the activity level of UGT1A1 in pancreatic cancer cells and in vivo. Here, we report a fluorescent probe, BCy-panc, for UGT1A1 imaging in cells and in vivo. Compared with other molecular probes, this probe is readily prepared, with high selectivity and sensitivity for the detection of UGT1A1. Our results show that BCy-panc rapidly detects UGT1A1 in pancreatic cancer. In addition, there is an urgent need for evidence to clarify the relationship between UGT1A1 and pancreatic cancer development. The present investigation found that the increase of UGT1A1 by chrysin was effective in inducing apoptosis in pancreatic cancer cells. These results indicate that the synergistic effect of chrysin and cisplatin at the cellular level is superior to that of cisplatin alone. The UGT1A1 level may be a biomarker for early diagnosis of cancer. Meanwhile, UGT1A1 plays a crucial role in pancreatic cancer, and the combination of chrysin and cisplatin may provide effective ideas for pancreatic cancer treatment.


Subject(s)
Fluorescent Dyes , Glucuronosyltransferase , Pancreatic Neoplasms , Pancreatic Neoplasms/diagnostic imaging , Humans , Glucuronosyltransferase/metabolism , Fluorescent Dyes/chemistry , Cell Line, Tumor , Animals , Apoptosis/drug effects , Optical Imaging/methods , Cisplatin/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry
7.
Pest Manag Sci ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662472

ABSTRACT

BACKGROUND: The use of unmanned aerial vehicles (UAVs) for the application of plant protection products (PPPs) in paddy fields is becoming increasingly prevalent worldwide. Despite its growing usage, UAV spraying for rice pest control faces practical challenges, including limited canopy penetration, uneven deposition, and significant spray drift. This study investigated the impact of two tank-mix adjuvants, Wonderful Rosin (Adjuvant-1) and Tiandun (Adjuvant-2), at six volume concentrations, on the spray liquid's physicochemical properties, spray drift, plant deposition, and the biological efficacy of rice insecticides using a quadrotor UAV sprayer. RESULTS: The physicochemical characteristics of the spray liquid influenced spray performance and biological efficacy. Incorporating Adjuvant-1 and Adjuvant-2 led to a decrease in surface tension and contact angle while increasing the viscosity of the spray solution. These alterations in surface tension and viscosity contributed to an optimized droplet size distribution, reduced spray drift, enhanced deposition uniformity and penetration, and improved control efficacy against the rice planthopper in UAV applications. The highest control efficacy was observed at a concentration of 0.5%, showing an improvement of 35.12% (Adjuvant-1) and 20.23% (Adjuvant-2) over applications without tank-mix adjuvant 7 days after treatment. CONCLUSION: The judicious selection of tank-mix adjuvants for UAV PPP applications can significantly enhance spray performance and biological efficacy in controlling rice insects. This study's findings offer valuable insights for integrating tank-mix adjuvants into UAV spraying applications. © 2024 Society of Chemical Industry.

8.
World J Clin Oncol ; 15(3): 391-410, 2024 Mar 24.
Article in English | MEDLINE | ID: mdl-38576597

ABSTRACT

BACKGROUND: Ferroptosis has recently been associated with multiple degenerative diseases. Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases. However, the association of iron proliferation-related genes with prognosis in HER2+ breast cancer (BC) patients is unclear. AIM: To identify and evaluate fresh ferroptosis-related biomarkers for HER2+ BC. METHODS: First, we obtained the mRNA expression profiles and clinical information of HER2+ BC patients from the TCGA and METABRIC public databases. A four-gene prediction model comprising PROM2, SLC7A11, FANCD2, and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort. Patients were stratified into high-risk and low-risk groups based on their median risk score, an independent predictor of overall survival (OS). Based on these findings, immune infiltration, mutations, and medication sensitivity were analyzed in various risk groupings. Additionally, we assessed patient prognosis by combining the tumor mutation burden (TMB) with risk score. Finally, we evaluated the expression of critical genes by analyzing single-cell RNA sequencing (scRNA-seq) data from malignant vs normal epithelial cells. RESULTS: We found that the higher the risk score was, the worse the prognosis was (P < 0.05). We also found that the immune cell infiltration, mutation, and drug sensitivity were different between the different risk groups. The high-risk subgroup was associated with lower immune scores and high TMB. Moreover, we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses. HRisk-HTMB patients had the worst prognosis, whereas LRisk-LTMB patients had the best prognosis (P < 0.0001). Analysis of the scRNA-seq data showed that PROM2, SLC7A11, and FANCD2 were significantly differentially expressed, whereas FH was not, suggesting that these genes are expressed mainly in cancer epithelial cells (P < 0.01). CONCLUSION: Our model helps guide the prognosis of HER2+ breast cancer patients, and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

9.
Sensors (Basel) ; 24(7)2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38610520

ABSTRACT

Robotic odor source localization (OSL) is a technology that enables mobile robots or autonomous vehicles to find an odor source in unknown environments. An effective navigation algorithm that guides the robot to approach the odor source is the key to successfully locating the odor source. While traditional OSL approaches primarily utilize an olfaction-only strategy, guiding robots to find the odor source by tracing emitted odor plumes, our work introduces a fusion navigation algorithm that combines both vision and olfaction-based techniques. This hybrid approach addresses challenges such as turbulent airflow, which disrupts olfaction sensing, and physical obstacles inside the search area, which may impede vision detection. In this work, we propose a hierarchical control mechanism that dynamically shifts the robot's search behavior among four strategies: crosswind maneuver, Obstacle-Avoid Navigation, Vision-Based Navigation, and Olfaction-Based Navigation. Our methodology includes a custom-trained deep-learning model for visual target detection and a moth-inspired algorithm for Olfaction-Based Navigation. To assess the effectiveness of our approach, we implemented the proposed algorithm on a mobile robot in a search environment with obstacles. Experimental results demonstrate that our Vision and Olfaction Fusion algorithm significantly outperforms vision-only and olfaction-only methods, reducing average search time by 54% and 30%, respectively.

10.
Cell Rep ; 43(4): 114120, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38625796

ABSTRACT

Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ monocyte-derived long-lived BAMs in a brain compression model and in a sepsis model after the initial disruption of homeostasis. Our study reveals that the short-lived CCR2+ monocytes transform into long-lived BAM-like cells at the CNS border and subsequently contribute to BAM populations.


Subject(s)
Brain , Macrophages , Monocytes , Receptors, CCR2 , Animals , Receptors, CCR2/metabolism , Monocytes/metabolism , Macrophages/metabolism , Mice , Brain/pathology , Brain/metabolism , Mice, Inbred C57BL , Homeostasis
11.
Sci Rep ; 14(1): 7363, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38548748

ABSTRACT

This article employs a plate with V-shape ribs inside a tube as turbulator to augment the heat transfer rate. The utilized vortex generators are double-winglets arranged in a V-shape placed on both sides of the plate. The proposed system's suggested working fluids are water-based hybrid nanofluids, including Al2O3-Cu/water, Cu-CuO/water, and Cu-TiO2/water. This work involves a numerical evaluation of the effects of the type and volume concentration of the examined hybrid nanofluids on the enhancement of heat transfer. The experimental results are used to validate the numerical model. It is worth mentioning that all the obtained numerical results are compared with the simple tube, without any turbulator (vortex generator) and in the presence of water instead of the hybrid nanofluids. Based on the numerical results, it can be concluded that all employed hybrid nanofluids showed improved thermal performance compared to pure water. Furthermore, the differences between the models are more substantial for higher Reynolds numbers than for lower Reynolds numbers. In Re = 30,000, the Cu-TiO2/water exhibits the lowest thermal performance improvement (augmentation of about 0.3%), while the Cu-CuO/water at Re = 50,000 exhibits the largest thermal performance improvement (augmentation of approximately 5.7%), in the case of ∅1 = ∅2 = 0.5%. For ∅1 = ∅2 = 1%, the Cu-TiO2/water at Re = 30,000 has the lowest thermal performance improvement (augmentation of around 1.1%), while the Cu-CuO/water at Re = 50,000 has the most thermal performance improvement (augmentation of roughly 8.7%). According to the augmentation of around 2.8% at Re = 30,000 for Cu-TiO2/water and approximately 10.8% at Re = 50,000 for Cu-CuO/water, the thermal performance increase in the scenario of ∅1 = ∅2 = 1.5% is the lowest. In Conclusion, the Cu-CuO/water hybrid nanofluid with a volume concentration of ∅1 = ∅2 = 1.5% has the greatest thermal performance value of all the hybrid nanofluids studied.

12.
Sci Total Environ ; 926: 172081, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38554961

ABSTRACT

Mature compost can promote the transformation of organic matter (OM) and reduce the emission of polluting gases during composting, which provides a viable approach to reduce the environmental impacts of biodegradable plastics (BPs). This study investigated the impact of mature compost on polybutylene adipate terephthalate (PBAT) degradation, greenhouse gas (GHG) emission, and microbial community structure during composting under two treatments with mature compost (MC) and without (CK). Under MC, visible plastic rupture was advanced from day 14 to day 10, and a more pronounced rupture was observed at the end of composting. Compared with CK, the degradation rate of PBAT in MC was increased by 4.44 % during 21 days of composting. Thermobifida, Ureibacillus, and Bacillus, as indicator species under MC treatment, played an important role in PBAT decomposition. Mature compost reduced the total global warming potential (GWP) by 25.91 % via inhibiting the activity of bacteria related to the production of CH4 and N2O. Functional Annotation of Prokaryotic Taxa (FAPROTAX) further revealed that mature compost addition increased relative abundance of bacteria related to multiple carbon (C) cycle functions such as methylotrophy, hydrocarbon degradation and cellulolysis, inhibited nitrite denitrification and denitrification, thus alleviating the emission of GHGs. Overall, mature compost, as an effective additive, exhibits great potential to simultaneously mitigate BP and GHG secondary pollution in co-composting of food waste and PBAT.


Subject(s)
Biodegradable Plastics , Composting , Greenhouse Gases , Refuse Disposal , Greenhouse Gases/analysis , Food Loss and Waste , Food , Soil/chemistry , Methane/analysis , Manure
13.
Nanoscale ; 16(15): 7341-7362, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38511991

ABSTRACT

Crude oil is one of the most widely used energy and industrial raw materials that is crucial to the world economy, and is used to produce various petroleum products. However, crude oil often spills during extraction, transportation and use, causing negative impacts on the environment. Thus, there is a high demand for products to remediate leaked crude oil. Among them, oleophilic and hydrophobic adsorbents can absorb crude oil through thermal effects and are research hotspots. In this review, we first present an overview of wettability theory, the heating principles of various thermal effects, and the theory of reducing crude oil viscosity by heating. Then we discuss adsorbents based on different heating methods including the photothermal effect, Joule heating effect, alternating magnetic field heating effect, and composite heating effect. Preparation methods and oil adsorption performance of adsorbents are summarized. Finally, the advantages and disadvantages of various heating methods are briefly summarized, as well as the prospects for future research.

14.
Nano Lett ; 24(10): 3133-3141, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38477056

ABSTRACT

Liquid manipulation is essential for daily life and modern industry, and it is widely used in various fields, including seawater desalination, microfluidic robots, and biomedical engineering. Nevertheless, the current research focuses on the manipulation of individual droplets. There are a few projects for water film management. Here, we proposed a facile method of wind-triggered water film self-sculpturing based on a heterogeneous wettability surface, which is achieved by the femtosecond laser direct writing technology and femtosecond laser deposition. Under the conditions of various airflow velocities and water film thicknesses, three distinct behaviors of the water film were analyzed. As a result, when the water film thickness is lower than 4.9 mm, the self-sculpture process will occur until the whole superhydrophobic surface dewetting. Four potential applications are demonstrated, including encryption, oil containers, reconfigurable patterning, and self-splitting devices. This work provides a new approach for manipulating a water film of fluid control engineering.

15.
bioRxiv ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38405754

ABSTRACT

Microglia actively survey the brain and dynamically interact with neurons to maintain brain homeostasis. Microglial Gi-protein coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, the impact of temporally activating microglial Gi signaling on microglial dynamics and neuronal activity in the homeostatic brain remains largely unknown. In this study, we employed Gi-based Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADD) to selectively and temporally modulate microglial Gi signaling pathway. By integrating this chemogenetic approach with in vivo two-photon imaging, we observed that exogenous activation of microglial Gi signaling transiently inhibited microglial process dynamics, reduced neuronal activity, and impaired neuronal synchronization. These altered neuronal functions were associated with a decrease in interactions between microglia and neuron somata. Altogether, this study demonstrates that acute, exogenous activation of microglial Gi signaling can regulate neuronal circuit function, offering a potential pharmacological target for neuromodulation through microglia.

16.
Heliyon ; 10(3): e24953, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38314265

ABSTRACT

Objective: Fungiform papillae contain taste buds and play a critical role in mastication and the gustatory system. In this study, we report a series of sequential observations of organogenesis of fungiform papillae in miniature pigs, as well as changes in the expression of BMP2, BMP4, Wnt5a, Sox2, and Notch1 signaling pathway components. Design: In this study, we investigated the spatiotemporal expression patterns of BMP, Wnt, Sox2 and Notch in the fungiform papillae of miniature pigs at the bud stage (E40), cap stage (E50) and bell stage (E60). Pregnant miniature pigs were obtained, and the samples were processed for histological staining. Immunohistochemistry and real-time PCR were used to detect the mRNA and protein expression levels of BMP2, BMP4, Wnt5a, Sox2, and Notch1. Results: At E40, fungiform papillae were present on the anterior two-thirds of the tongue in a specific array and pattern. The fungiform papillae were enlarged and basically developed at E50 and were largest at the earlier stage (E60). Most of the BMP2 was concentrated in the epithelial layer and the connective tissue core of the fungal papilloma and gradually accumulated from E40-E60. BMP-4 was weakly expressed in the fungiform papillae epithelia, but BMP-4-positive cells were also observed in the developing tongue muscle at E50 and E60. Wnt5a-positive cells were observed in the fungiform papillae epithelia and developing tongue muscle at all three time points. Sox2-positive cells were observed only in fungiform papillae epithelial cells, and Notch1-positive cells could not be detected. Conclusions: This study provides primary data regarding the morphogenesis and expression of developmental signals in the fungiform papillae of miniature pigs, establishing a foundation for further research in both this model and humans.

17.
bioRxiv ; 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38260601

ABSTRACT

In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about the role TREM2 plays in epileptogenesis. To investigate this, we utilized TREM2 knockout (KO) mice within the murine intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both acute status epilepticus and spontaneous recurrent seizures characteristic of chronic focal epilepsy. Mechanistically, phagocytic clearance of damaged neurons by microglia was impaired in TREM2 KO mice and the reduced phagocytic capacity correlated with increased spontaneous seizures. Analysis of human tissue from patients who underwent surgical resection for drug resistant temporal lobe epilepsy also showed a negative correlation between microglial phagocytic activity and focal to bilateral tonic-clonic generalized seizure history. These results indicate that microglial TREM2 and phagocytic activity may be important to epileptogenesis and the progression of focal temporal lobe epilepsy.

19.
Mol Neurobiol ; 61(1): 224-238, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37597108

ABSTRACT

Aging of the brain usually leads to the decline of neurological processes and is a major risk factor for various neurodegenerative diseases, including sleep disturbances and cognitive decline. Adipose tissue exosomes, as adipocyte-derived vesicles, may mediate the regulatory processes of adipose tissue on other organs, including the brain; however, the regulatory mechanisms remain unclear. We analyzed the sleep-wake behavior of young (10 days) and old (40 days) Drosophila and found that older Drosophila showed increased sleep fragmentation, which is similar to mammalian aging characteristics. To investigate the cross-tissue regulatory mechanisms of adiposity on brain aging, we extracted 10-day and 40-day Drosophila adipose tissue exosomes and identified circRNAs with age-dependent expression differences by RNA-seq and differential analysis. Furthermore, by combining data from 3 datasets of the GEO database (GSE130158, GSE24992, and GSE184559), circ_sxc that was significantly downregulated with age was finally screened out. Moreover, dme-miR-87-3p, a conserved target of circ_sxc, accumulates in the brain with age and exhibits inhibitory effects in predicted binding relationships with neuroreceptor ligand genes. In summary, the current study showed that the Drosophila brain could obtain circ_sxc by uptake of adipose tissue exosomes which crossed the blood-brain barrier. And circ_sxc suppressed brain miR-87-3p expression through sponge adsorption, which in turn regulated the expression of neurological receptor ligand proteins (5-HT1B, GABA-B-R1, Rdl, Rh7, qvr, NaCP60E) and ensured brain neuronal synaptic signaling normal function of synaptic signaling. However, with aging, this regulatory mechanism is dysregulated by the downregulation of the adipose exosome circ_sxc, which contributes to the brain exhibiting sleep disturbances and other "aging" features.


Subject(s)
Exosomes , MicroRNAs , Animals , Lipid Droplets , Ligands , Brain , Adipose Tissue , Aging , Drosophila , MicroRNAs/genetics , Mammals
20.
IEEE Trans Pattern Anal Mach Intell ; 46(2): 1199-1211, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37903051

ABSTRACT

Offline reinforcement learning (RL) harnesses the power of massive datasets for resolving sequential decision problems. Most existing papers only discuss defending against out-of-distribution (OOD) actions while we investigate a broader issue, the false correlations between epistemic uncertainty and decision-making, an essential factor that causes suboptimality. In this paper, we propose falSe COrrelation REduction (SCORE) for offline RL, a practically effective and theoretically provable algorithm. We empirically show that SCORE achieves the SoTA performance with 3.1x acceleration on various tasks in a standard benchmark (D4RL). The proposed algorithm introduces an annealing behavior cloning regularizer to help produce a high-quality estimation of uncertainty which is critical for eliminating false correlations from suboptimality. Theoretically, we justify the rationality of the proposed method and prove its convergence to the optimal policy with a sublinear rate under mild assumptions.

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