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Precisely defining and mapping all cytosine (C) positions and their clusters, known as CpG islands (CGIs), as well as their methylation status, are pivotal for genome-wide epigenetic studies, especially when population-centric reference genomes are ready for timely application. Here, we first align the two high-quality reference genomes, T2T-YAO and T2T-CHM13, from different ethnic backgrounds in a base-by-base fashion and compute their genome-wide density-defined and position-defined CGIs. Second, by mapping some representative genome-wide methylation data from selected organs onto the two genomes, we find that there are about 4.7%-5.8% sequence divergency of variable categories depending on quality cutoffs. Genes among the divergent sequences are mostly associated with neurological functions. Moreover, CGIs associated with the divergent sequences are significantly different with respect to CpG density and observed CpG/expected CpG (O/E) ratio between the two genomes. Finally, we find that the T2T-YAO genome not only has a greater CpG coverage than that of the T2T-CHM13 genome when whole-genome bisulfite sequencing (WGBS) data from the European and American populations are mapped to each reference, but also shows more hyper-methylated CpG sites as compared to the T2T-CHM13 genome. Our study suggests that future genome-wide epigenetic studies of the Chinese populations rely on both acquisition of high-quality methylation data and subsequent precision CGI mapping based on the Chinese T2T reference.
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Ilhas de CpG , Metilação de DNA , Genoma Humano , Ilhas de CpG/genética , Metilação de DNA/genética , Humanos , Genoma Humano/genética , Mapeamento Cromossômico/métodosRESUMO
To obtain enhanced physical and biological properties, various nanoparticles are typically assembled into hybrid nanoparticles through the binding of multiple homologous DNA strands to their complementary counterparts, commonly referred to as homomultivalent assembly. However, the poor binding affinity and limited controllability of homomultivalent disassembly restrict the assembly yield and dynamic functionality of the hybrid nanoparticles. To achieve a higher binding affinity and flexible assembly choice, we utilized the paired heteromultivalency DNA to construct hybrid nanoparticles and demonstrate their excellent assembly characteristics and dynamic applications. Specifically, through heteromultivalency, DNA-functionalized magnetic beads (MBs) and gold nanoparticles (AuNPs) were efficiently assembled. By utilizing ICP-MS, the assembly efficiency of AuNPs on MBs was directly monitored, enabling quantitative analysis and optimization of heteromultivalent binding events. As a result, the enhanced assembly yield is primarily attributed to the fact that heteromultivalency allows for the maximization of effective DNA probes on the surface of nanoparticles, eliminating steric hindrance interference. Subsequently, with external oligonucleotides as triggers, it was revealed that the disassembly mechanism of hybrid nanoparticles was initiated, which was based on an increased local concentration rather than toehold-mediated displacement of paired heteromultivalency DNA probes. Capitalizing on these features, an output platform was then established based on ICP-MS signals that several Boolean operations and analytical applications can be achieved by simply modifying the design sequences. The findings provide new insights into DNA biointerface interaction, with potential applications to complex logic operations and the construction of large DNA nanostructures.
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DNA , Ouro , Espectrometria de Massas , Nanopartículas Metálicas , Ouro/química , DNA/química , Nanopartículas Metálicas/químicaRESUMO
Solar-driven carbon dioxide (CO2) methanation holds significant research value in the context of carbon emission reduction and energy crisis. However, this eight-electron catalytic reaction presents substantial challenges in catalytic activity and selectivity. In this regard, researchers have conducted extensive exploration and achieved significant developments. This review provides an overview of the recent advances and challenges in efficient selective photocatalytic CO2 methanation. It begins by discussing the fundamental principles and challenges in detail, analyzing strategies for improving the efficiency of photocatalytic CO2 conversion to CH4 comprehensively. Subsequently, it outlines the recent applications and advanced characterization methods for photocatalytic CO2 methanation. Finally, this review highlights the prospects and opportunities in this area, aiming to inspire CO2 conversion into high-value CH4 and shed light on the research of catalytic mechanisms.
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Artificial photosynthesis for hydrogen peroxide (H2O2) presents a sustainable and environmentally friendly approach to generate clean fuel and chemicals. However, the catalytic activity is hindered by challenges such as severe charge recombination, insufficient active sites, and poor selectivity. Here, a robust strategy is proposed to regulate the electronic structure of catalyst by the collaborative effect of defect engineering and dopant. The well designed oxygen-doped CdS nanorods with S2- defects and Cd2+ 4d10 electron configuration (CdS-O,Sv) is successfully synthesized, and the Cd2+ active sites around S defects or oxygen atoms exhibit rapid charge separation, suppressed carrier recombination, and enhanced charge utilization. Consequently, a remarkable H2O2 production rate of 1.62 mmol g-1 h-1 under air conditions is acquired, with an apparent quantum yield (AQY) of 9.96% at a single wavelength of 450 nm. This work provides valuable insights into the synergistic effect between defect and doping on catalytic activity.
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Using Li2S cathodes instead of S cathodes presents an opportunity to pair them with Li-free anodes (e.g., graphite), thereby circumventing anode-related issues, such as poor reversibility and safety, encountered in Li-S batteries. However, the moisture-sensitive nature of Li2S causes the release of hazardous H2S and the formation of insulative by-products, increasing the manufacturing difficulty and adversely affecting cathode performance. Here, Li4SnS4, a Li+ conductor that is air-stable according to the hard-soft acid-base principle, is formed in situ and uniformly on Li2S particles because Li2S itself participates in Li4SnS4 formation. When exposed to air (20% relative humidity), the protective Li4SnS4 layer maintains its components and structure, thus contributing to the enhanced stability of the Li2S@Li4SnS4 composite. In addition, the Li4SnS4 layer can accelerate the sluggish conversion of Li2S because of its favorable interfacial charge transfer, and continuously confine lithium polysulfides owing to its integrity during electrochemical processes. A graphite-Li2S pouch cell containing a Li2S@Li4SnS4 cathode is constructed, which shows stable cyclability with 97% capacity retention after 100 cycles. Hence, combining a desirable air-stable Li2S cathode and a highly reversible Li-free configuration offers potential practical applications of graphite-Li2S full cells.
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OBJECTIVE: Neonatal hypoxic-ischemic brain damage (HIBD) can have long-term implications on patients' physical and mental health, yet the available treatment options are limited. Recent research has shown that low-intensity pulsed ultrasound (LIPUS) holds promise for treating neurodegenerative diseases and traumatic brain injuries. Our objective was to explore the therapeutic potential of LIPUS for HIBD. METHODS: Due to the lack of a suitable animal model for neonatal HIBD, we will initially simulate the therapeutic effects of LIPUS on neuronal cells under oxidative stress and neuroinflammation using cell experiments. Previous studies have investigated the biologic responses following intracranial injection of 6-hydroxydopamine (6-OHDA). In this experiment, we will focus on the biologic effects produced by LIPUS treatment on neuronal cells (specifically, SH-SY5Y cells) without the presence of other neuroglial cell assistance after stimulation with 6-OHDA. RESULTS: We found that (i) pulsed ultrasound exposure, specifically three-intermittent sonication at intensities ranging from 0.1 to 0.5 W/cm², did not lead to a significant decrease in viability among SH-SY5Y cells; (ii) LIPUS treatment exhibited a positive effect on cell viability, accompanied by an increase in glial cell-derived neurotrophic factor (GDNF) levels and a decrease in caspase three levels; (iii) the administration of 6-OHDA had a significant impact on cell viability, resulting in a decrease in both brain cell-derived neurotrophic factor (BDNF) and GDNF levels, while concurrently elevating caspase three and matrix metalloproteinase-9 (MMP-9) levels; and (iv) LIPUS treatment demonstrated its potential to alleviate the changes induced by 6-OHDA, particularly in the levels of BDNF, GDNF, and tyrosine hydroxylase (TH). CONCLUSION: LIPUS treatment may possess partial therapeutic capabilities for SH-SY5Y cells damaged by 6-OHDA neurotoxicity. Our findings enhance our understanding of the effects of LIPUS treatment on cell viability and its modulation of key factors involved in the pathophysiology of HIBD and show the promising potential of LIPUS as an alternative therapeutic approach for neonates with HIBD.
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Produtos Biológicos , Neuroblastoma , Animais , Recém-Nascido , Humanos , Fator Neurotrófico Derivado do Encéfalo , Oxidopamina , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Ondas Ultrassônicas , CaspasesRESUMO
BACKGROUND AND HYPOTHESIS: Treatment of schizophrenia remains a major challenge. Recent studies have focused on glutamatergic signaling hypoactivity through N-methyl-D-aspartate (NMDA) receptors. Low-intensity pulsed ultrasound (LIPUS) improves behavioral deficits and ameliorates neuropathology in dizocilpine (MK-801)-treated rats. The aim of this study was to investigate the efficacy of LIPUS against psychiatric symptoms and anxiety-like behaviors. STUDY DESIGN: Rats assigned to 4 groups were pretreated with or without LIPUS for 5 days. The open field and prepulse inhibition tests were performed after saline or MK-801 (0.3 mg/kg) administration. Then, the neuroprotective effects of LIPUS on the MK-801-treated rats were evaluated using western blotting and immunohistochemical staining. STUDY RESULTS: LIPUS stimulation of the prefrontal cortex (PFC) prevented deficits in locomotor activity and sensorimotor gating and improved anxiety-like behavior. MK-801 downregulated the expression of NR1, the NMDA receptor, in rat medial PFC (mPFC). NR1 expression was significantly higher in animals receiving LIPUS pretreatment compared to those receiving only MK-801. In contrast, a significant increase in c-Fos-positive cells in the mPFC and ventral tegmental area was observed in the MK-801-treated rats compared to those receiving only saline; this change was suppressed by pretreatment with LIPUS. CONCLUSIONS: This study provides new evidence for the role of LIPUS stimulation in regulating the NMDA receptor and modulating c-Fos activity, which makes it a potentially valuable antipsychotic treatment for schizophrenia.
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Esquizofrenia , Animais , Ratos , Esquizofrenia/induzido quimicamente , Maleato de Dizocilpina/farmacologia , Receptores de N-Metil-D-Aspartato , Ansiedade , Córtex Pré-FrontalRESUMO
Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the intestinal tract. There is currently no effective cure for IBD. The aim of this study was to evaluate the protective effect of low-intensity pulsed ultrasound (LIPUS) on lipopolysaccharide (LPS)-induced intestinal damage in a C57BL/6 mouse model. Colonic inflammation was induced by LPS injection (0.75 mg/kg, i.p.) for 7 days. A 1.0 MHz ultrasound transducer was used with a duty cycle of 5% and a repetition frequency of 1 Hz. LIPUS was applied to the abdominal region for 15 min/day from days 1 to 6 at both intensity of 0.5 W/cm2 or 1.0 W/cm2. Colonic samples were collected for macroscopic and westerm blotting analysis. First, the optimal dose of LPS for experiments was investigated. Our results demonstrated that LIPUS alleviates colonic damage by reducing colon shortening and increasing the levels of tight junction proteins such as Occludin and ZO-1. These findings show that abdominal LIPUS stimulation may be a novel therapeutic strategy for IBD through enhancement of tight junction protein levels and attenuation of colonic length.
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Doenças Inflamatórias Intestinais , Lipopolissacarídeos , Camundongos , Animais , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Colo , Inflamação/metabolismoRESUMO
Purpose: This study aimed to explore the clinical efficacy of transarterial chemoembolization (TACE) in combination with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (triple therapy) compared to TACE alone (monotherapy) for advanced hepatocellular carcinoma (HCC). Material and Methods: Data of consecutive advanced HCC patients receiving triple therapy or monotherapy at our center between January 2019 and December 2022 were collected and retrospectively analyzed. Propensity score matching (PSM) and subgroup analyses were performed to reduce the bias between the two groups. The primary outcomes of the study were the overall survival (OS) and progression-free survival (PFS). The secondary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: A total of 104 patients were enrolled in this study: 41 in the triple therapy group and 63 in the monotherapy group. After PSM analysis, each group included 37 patients. The median OS and PFS were significantly longer in the triple therapy group than in the monotherapy group in the whole cohort (median OS, 18.8 vs 11.7 months, P = 0.022; median PFS, 10.5 vs 6.4 months, P = 0.012) and after PSM (median OS, 19.6 vs 12.5 months, P = 0.030; median PFS, 10.5 vs 6.7 months, P = 0.008). Furthermore, the treatment modality was an independent prognostic factor for OS (hazard ratio [HR]: 0.449, 95% confidence interval [CI]: 0.240-0.840, P = 0.012) and PFS (HR: 0.406, 95% CI: 0.231-0.713, P = 0.002) according to the multivariate cox regression analysis. A greater ORR was also observed in the triple therapy group (ORR: 56.7% vs 32.4%, P = 0.035). No significant difference was observed in DCR between the two groups (83.7% vs 72.9%, P = 0.259). Conclusion: The triple therapy was superior to the monotherapy regarding OS, PFS, and ORR of advanced HCC patients.
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The number of patients with dementia grows rapidly as the global population ages, which posits tremendous health-care burden to the society. Only cholinesterase inhibitors and a N-methyl-D-aspartate receptor antagonist have been approved for treating patients with Alzheimer's disease (AD), and their clinical effects remained limited. Medical devices serve as an alternative therapeutic approach to modulating neural activities and enhancing cognitive function. Four major brain stimulation technologies including deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial ultrasound stimulation (TUS) have been applied to AD in a clinical trial setting. DBS allows electrical stimulation at the specified nucleus but remains resource-demanding, and after all, an invasive surgery; whereas TMS and tDCS are widely available and affordable but less ideal with respect to localization. The unique physical property of TUS, on the other hand, allows both thermal and mechanical energy to be transduced and focused for neuromodulation. In the context of dementia, using focused ultrasound to induce blood-brain barrier opening for delivering drugs and metabolizing amyloid protein has drawn great attention in recent years. Furthermore, low-intensity pulsed ultrasound has demonstrated its neuroprotective effects in both in vitro and in vivo studies, leading to ongoing clinical trials for AD. The potential and limitation of transcranial brain stimulation for treating patients with dementia would be discussed in this review.
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BACKGROUND: Intracerebral hemorrhage (ICH) is a condition associated with high morbidity and mortality, and glia-mediated inflammation is a major contributor to neurological deficits. However, there is currently no proven effective treatment for clinical ICH. Recently, low-intensity pulsed ultrasound (LIPUS), a non-invasive method, has shown potential for neuroprotection in neurodegenerative diseases. This study aimed to investigate the neuroprotective effects and potential mechanisms of LIPUS on glia-mediated inflammation in ICH. METHODS: This study used 289 mice to investigate the effects of LIPUS on ICH. ICH was induced by injecting bacterial collagenase (type VII-S; 0.0375 U) into the striatum of the mice. LIPUS was applied noninvasively for 3 days, including a 2-h-delayed intervention to mimic clinical usage. The study evaluated neurological function, histology, brain water content, hemoglobin content, MRI, and protein expression of neurotrophic factors, inflammatory molecules, and apoptosis. In vitro studies investigated glia-mediated inflammation by adding thrombin (10 U/mL) or conditioned media to primary and cell line cultures. The PI3K inhibitor LY294002 was used to confirm the effects of PI3K/Akt signaling after LIPUS treatment. RESULTS: LIPUS treatment improved neurological deficits and reduced tissue loss, edema, and neurodegeneration after ICH. The protective effects of LIPUS resulted from decreased glia-mediated inflammation by inhibiting PI3K/Akt-NF-κB signaling, which reduced cytokine expression and attenuated microglial activation-induced neuronal damage in vitro. CONCLUSIONS: LIPUS treatment improved neurological outcomes and reduced glia-mediated inflammation by inhibiting PI3K/Akt-NF-κB signaling after ICH. LIPUS may provide a non-invasive potential management strategy for ICH.
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NF-kappa B , Fosfatidilinositol 3-Quinases , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt , Neuroglia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/terapiaRESUMO
Plague, caused by Yersinia pestis, is a zoonotic disease that can reemerge and cause outbreaks following decades of latency in natural plague foci. However, the genetic diversity and spread pattern of Y. pestis during these epidemic-silent cycles remain unclear. In this study, we analyze 356 Y. pestis genomes isolated between 1952 and 2016 in the Yunnan Rattus tanezumi plague focus, China, covering two epidemic-silent cycles. Through high-resolution genomic epidemiological analysis, we find that 96% of Y. pestis genomes belong to phylogroup 1.ORI2 and are subdivided into two sister clades (Sublineage1 and Sublineage2) characterized by different temporal-spatial distributions and genetic diversity. Most of the Sublineage1 strains are isolated from the first epidemic-silent cycle, while Sublineage2 strains are predominantly from the second cycle and revealing a west to east spread. The two sister clades evolved in parallel from a common ancestor and independently lead to two separate epidemics, confirming that the pathogen responsible for the second epidemic following the silent interval is not a descendant of the causative strain of the first epidemic. Our results provide a mechanism for defining epidemic-silent cycles in natural plague foci, which is valuable in the prevention and control of future plague outbreaks.
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Epidemias , Peste , Yersinia pestis , Animais , Ratos , Peste/epidemiologia , Yersinia pestis/genética , China/epidemiologia , Genótipo , GenômicaRESUMO
INTRODUCTION: Activated microglia can be polarized to the pro-inflammatory M1 phenotype and the anti-inflammatory M2 phenotype. Low-intensity pulsed ultrasound (LIPUS) can attenuate pro-inflammatory responses in activated microglia. OBJECTIVE: This study aimed to investigate the effects of LIPUS on M1/M2 polarization of microglial cells and the regulatory mechanisms associated with signaling pathways. METHODS: BV-2 microglial cells were stimulated by lipopolysaccharide (LPS) to an M1 phenotype or by interleukin-4 (IL-4) to an M2 phenotype. Some microglial cells were exposed to LIPUS, while others were not. M1/M2 marker mRNA and protein expression were measured using real-time polymerase chain reaction and western blot, respectively. Immunofluorescence staining was performed to determine inducible nitric oxide synthase (iNOS)-/arginase-1 (Arg-1)- and CD68-/CD206-positive cells. RESULTS: LIPUS treatment significantly attenuated LPS-induced increases in inflammatory markers (iNOS, tumor necrosis factor-α, interleukin-1ß, and interleukin-6) as well as the expression of cell surface markers (CD86 and CD68) of M1-polarized microglia. In contrast, LIPUS treatment significantly enhanced the expression of M2-related markers (Arg-1, IL-10, and Ym1) and membrane protein (CD206). LIPUS treatment prevented M1 polarization of microglia and enhanced or sustained M2 polarization by regulating M1/M2 polarization through the signal transducer and activator of transcription 1/STAT6/peroxisome proliferator-activated receptor gamma pathways. CONCLUSIONS: Our findings suggest that LIPUS inhibits microglial polarization and switches microglia from the M1 to the M2 phenotype.
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Microglia , PPAR gama , Humanos , Lipopolissacarídeos/farmacologia , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/farmacologia , Transdução de Sinais , Inflamação/metabolismo , Fator de Transcrição STAT6RESUMO
Systemic inflammation is associated with intestinal inflammation and neuroinflammation by imbalancing the gut-brain axis. Low-intensity pulsed ultrasound (LIPUS) has neuroprotective and anti-inflammatory effects. This study explored LIPUS's neuroprotective effects against lipopolysaccharide (LPS)-induced neuroinflammation through transabdominal stimulation. Male C57BL/6J mice were intraperitoneally injected with LPS (0.75 mg/kg) daily for seven days, and abdominal LIPUS was applied to the abdominal area for 15 min/day during the last six days. One day after the last LIPUS treatment, biological samples were collected for microscopic and immunohistochemical analysis. Histological examination showed that LPS administration leads to tissue damage in the colon and brain. Transabdominal LIPUS stimulation attenuated colonic damage, reducing histological score, colonic muscle thickness, and villi shortening. Furthermore, abdominal LIPUS reduced hippocampal microglial activation (labeled by ionized calcium-binding adaptor molecule-1 [Iba-1]) and neuronal cell loss (labeled by microtubule-associated protein 2 [MAP2]). Moreover, abdominal LIPUS attenuated the number of apoptotic cells in the hippocampus and cortex. Altogether, our results indicate that abdominal LIPUS stimulation attenuates LPS-induced colonic inflammation and neuroinflammation. These findings provide new insights into the treatment strategy for neuroinflammation-related brain disorders and may facilitate method development through the gut-brain axis pathway.
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Lipopolissacarídeos , Neuroproteção , Animais , Camundongos , Masculino , Lipopolissacarídeos/toxicidade , Doenças Neuroinflamatórias , Camundongos Endogâmicos C57BL , Inflamação/induzido quimicamente , Inflamação/terapia , Inflamação/metabolismoRESUMO
Developing electrocatalysts based on transition-metal carbides that can be utilized for commercial water splitting is a challenging endeavor. To address this challenge, we employed a novel approach that merged phase-inversion tape-casting and sintering, subsequently implementing a simple and efficient electrodeposition process, to synthesize Ni-activated and Ni-P-activated titanium carbide (Ni/TiC, Ni-P/TiC) ceramic electrodes as water splitting catalytic cathodes and anodes. These self-supported Ni/TiC and Ni-P/TiC electrodes are binder-free with abundant finger-like pores, which contribute to the formation of highly conductive skeleton and more exposed active sites for direct water splitting. These catalysts exhibit outstanding performance, superior to many reported bifunctional nickel-based catalysts supported on other substrates. Moreover, the exceptional electrocatalytic performance of the Ni/TiC and Ni-P/TiC catalysts is attributed to the synergistic effect between Ni oxides (phosphides) and TiC, as revealed by density functional theory (DFT) calculations. This self-template strategy paves the way for fabricating industrially applicable electrodes to generate hydrogen and oxygen through water splitting.
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AIM: Inflammatory bowel disease (IBD) may be a risk factor in the development of brain inflammation. It has been demonstrated noninvasive neuromodulation through sub-organ ultrasound stimulation. The purpose of this study was to investigate whether abdominal low-intensity pulsed ultrasound (LIPUS) alleviates lipopolysaccharide (LPS)-induced cortical inflammation via inhibition of colonic inflammation. MATERIALS AND METHODS: Colonic and cortical inflammation was induced in mice by LPS (0.75 mg/kg, i.p. injection) for 7 days, followed by application of LIPUS (0.5 and 1.0 W/cm2) to the abdominal area for 6 days. Biological samples were collected for Western blot analysis, gelatin zymography, colon length measurement, and histological evaluation. KEY FINDINGS: LIPUS treatment significantly attenuated LPS-induced increases in IL-6, IL-1ß, COX-2, and cleaved caspase-3 expression in the colon and cortex of mice. Moreover, LIPUS significantly increased the levels of tight junction proteins in the epithelial barrier in the mouse colon and cortex with LPS-induced inflammation. Compared to the group treated only with LPS, the LIPUS-treated groups showed decreased muscle thickness and increased crypt length and colon length. Furthermore, LIPUS treatment reduced inflammation by inhibiting the LPS-induced activation of TLR4/NF-κB inflammatory signaling in the brain. SIGNIFICANCE: We found that LIPUS alleviated LPS-induced colonic and cortical inflammation through abdominal stimulation of mice. These results suggest that abdominal LIPUS stimulation may be a novel therapeutic strategy against neuroinflammation via enhancement of tight junction protein levels and inhibition of inflammatory responses in the colon.
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NF-kappa B , Animais , Camundongos , Inflamação/induzido quimicamente , Inflamação/terapia , Lipopolissacarídeos/toxicidade , Doenças Neuroinflamatórias , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismoRESUMO
Finding highly efficient hydrogen evolution reaction (HER) catalysts is pertinent to the ultimate goal of transformation into a net-zero carbon emission society. The design principles for such HER catalysts lie in the well-known structure-property relationship, which guides the synthesis procedure that creates catalyst with target properties such as catalytic activity. Here we report a general strategy to synthesize 10 kinds of single-atom-doped CoSe2-DETA (DETA = diethylenetriamine) nanobelts. By systematically analyzing these products, we demonstrate a volcano-shape correlation between HER activity and Co atomic configuration (ratio of Co-N bonds to Co-Se bonds). Specifically, Pb-CoSe2-DETA catalyst reaches current density of 10 mA cm-2 at 74 mV in acidic electrolyte (0.5 M H2SO4, pH ~0.35). This striking catalytic performance can be attributed to its optimized Co atomic configuration induced by single-atom doping.
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The use of non-solvating, or as-called sparingly-solvating, electrolytes (NSEs), is regarded as one of the most promising solutions to the obstacles to the practical applications of Li-S batteries. However, it remains a puzzle that long-life Li-S batteries have rarely, if not never, been reported with NSEs, despite their good compatibility with Li anode. Here, we find the capacity decay of Li-S batteries in NSEs is mainly due to the accumulation of the dead Li2 S at the cathode side, rather than the degradation of the anodes or electrolytes. Based on this understanding, we propose an electrochemical strategy to reactivate the accumulated Li2 S and revive the dead Li-S batteries in NSEs. With such a facile approach, Li-S batteries with significantly improved cycling stability and accelerated dynamics are achieved with diglyme-, acetonitrile- and 1,2-dimethoxyethane-based NSEs. Our finding may rebuild the confidence in exploiting non-solvating Li-S batteries with practical competitiveness.
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It has been shown that transcranial ultrasound stimulation (TUS) is capable of attenuating myelin loss and providing neuroprotection in animal models of brain disorders. In this study, we investigated the ability of TUS to promote remyelination in the lysolecithin (LPC)-induced local demyelination in the hippocampus. Demyelination was induced by the micro-injection of 1.5 µL LPC (1%) into the rat hippocampus and the treated group received daily TUS for 5 or 12 days. Magnetic resonance imaging techniques, including magnetization transfer ratio (MTR) and T2-weighted imaging, were used to longitudinally characterize the demyelination model. Furthermore, the therapeutic effects of TUS on LPC-induced demyelination were assessed by Luxol fast blue (LFB) staining. Our data revealed that reductions in MTR values observed during demyelination recover almost completely upon remyelination. The MTR values in demyelinated lesions were significantly higher in TUS-treated rats than in the LPC-only group after undergoing TUS. Form histological observation, TUS significantly reduced the size of demyelinated lesion 7 days after LPC administration. This study demonstrated that MTR was a sensitive and reproducible quantitative marker to assess remyelination process in vivo during TUS treatment. These findings might open new promising treatment strategies for demyelinating diseases such as multiple sclerosis.
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Doenças Desmielinizantes , Esclerose Múltipla , Remielinização , Ratos , Animais , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/terapia , Esclerose Múltipla/patologia , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/terapia , Lisofosfatidilcolinas/toxicidade , Modelos Animais , Bainha de Mielina , Modelos Animais de DoençasRESUMO
In terms of mortality and survival, pancreatic cancer is one of the worst malignancies. Known as a unique type of programmed cell death, cuprotosis contributes to tumor cell growth, angiogenesis, and metastasis. Cuprotosis programmed-cell-death-related lncRNAs (CRLs) have been linked to PAAD, although their functions in the tumor microenvironment and prognosis are not well understood. This study included data from the TCGA-PAAD cohort. Random sampling of PAAD data was conducted, splitting the data into two groups for use as a training set and test set (7:3). We searched for differentially expressed genes that were substantially linked to prognosis using univariate Cox and Lasso regression analysis. Through the use of multivariate Cox proportional risk regression, a risk-rating system for prognosis was developed. Correlations between the CRL signature and clinicopathological characteristics, tumor microenvironment, immunotherapy response, and chemotherapy sensitivity were further evaluated. Lastly, qRT-PCR was used to compare CRL expression in healthy tissues to that in tumors. Some CRLs are thought to have strong correlations with PAAD outcomes. These CRLs include AC005332.6, LINC02041, LINC00857, and AL117382.1. The CRL-based signature construction exhibited outstanding predictive performance and offers a fresh approach to evaluating pre-immune effectiveness, paving the way for future studies in precision immuno-oncology.