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Electrical stimulation holds promise for enhancing neuronal differentiation of neural stem cells to treat traumatic brain injury. However, once the stem cells leave the stimulating material and migrate post transplantation, electrical stimulation on them is diminished. Here, we wrap the stem cells with wireless electrical nanopatches, the conductive graphene nanosheets. Under electromagnetic induction, electrical stimulation can thus be applied in-situ to individual nanopatch-wrapped stem cells on demand, stimulating their neuronal differentiation through a MAPK/ERK signaling pathway. Consequently, 41% of the nanopatch-wrapped stem cells differentiate into functional neurons in 5 days, as opposed to only 16.3% of the unwrapped ones. The brain injury male mice implanted with the nanopatch-wrapped stem cells and exposed to a rotating magnetic field 30 min/day exhibit significant recovery of brain tissues, behaviors, and cognitions, within 28 days. This study opens up an avenue to individualized electrical stimulation of transplanted stem cells for treating neurodegenerative diseases.
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Lesões Encefálicas Traumáticas , Diferenciação Celular , Células-Tronco Neurais , Transplante de Células-Tronco , Animais , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/patologia , Masculino , Camundongos , Células-Tronco Neurais/transplante , Células-Tronco Neurais/citologia , Transplante de Células-Tronco/métodos , Grafite/química , Estimulação Elétrica , Tecnologia sem Fio , Neurônios , Humanos , Encéfalo , Nanoestruturas/químicaRESUMO
α-Actinins play crucial roles in cytoskeletal mechanobiology by acting as force-bearing structural modules that orchestrate and sustain the cytoskeletal framework, serving as pivotal hubs for diverse mechanosensing proteins. The mechanical stability of α-actinin dimer, a determinant of its functional state, remains largely unexplored. Here, we directly quantify the force-dependent lifetimes of homo- and hetero-dimers of human α-actinins, revealing an ultra-high mechanical stability of the dimers associated with > 100 seconds lifetime within 40 pN forces under shear-stretching geometry. Intriguingly, we uncover that the strong dimer stability is arisen from much weaker sub-domain pair interactions, suggesting the existence of distinct dimerized functional states of the dimer, spanning a spectrum of mechanical stability, with the spectrin repeats (SRs) in folded or unfolded conformation. In essence, our study supports a potent mechanism for building strength in biomolecular dimers through weak, multiple sub-domain interactions, and illuminates multifaceted roles of α-actinin dimers in cytoskeletal mechanics and mechanotransduction.
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Actinina , Multimerização Proteica , Humanos , Actinina/metabolismo , Actinina/química , Citoesqueleto/metabolismo , Mecanotransdução Celular , Domínios Proteicos , Imagem Individual de Molécula/métodosRESUMO
Temporomandibular joint osteoarthritis (TMJ OA) is characterized by the degeneration of cartilage and subchondral bone. In this study, we observed a significant increase in cell-free DNA (cfDNA) levels during the progression of TMJ OA. Bioinformatics analysis identified TLR9 as a pivotal molecule in TMJ OA pathogenesis. The polyamidoamine (PAMAM) dendrimer characterized by a well-structured, highly branched, and reactive nature, exhibits robust binding and clearance capabilities for cfDNA. However, the abundant amino groups on the surface of PAMAM lead to its inherent toxicity. To mitigate this, PEG-5000 was conjugated to the surface of PAMAM dendrimers, enhancing safety. Our results indicate that PEG-PAMAM effectively inhibits the upregulation of the TLR9 protein in TMJ OA, significantly suppressing the activation of the p-IκBα/p-NF-κB signaling pathway and subsequently decreasing chondrocyte inflammation and apoptosis, as evidenced by both in vivo and in vitro experiments. We conclude that PEG-PAMAM is a safe and effective material for in vivo applications, offering a promising therapeutic strategy for TMJ OA by targeting cfDNA clearance.
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Ácidos Nucleicos Livres , Dendrímeros , Osteoartrite , Polietilenoglicóis , Articulação Temporomandibular , Dendrímeros/química , Dendrímeros/farmacologia , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Osteoartrite/metabolismo , Animais , Polietilenoglicóis/química , Articulação Temporomandibular/patologia , Articulação Temporomandibular/efeitos dos fármacos , Articulação Temporomandibular/metabolismo , Adsorção , Humanos , Receptor Toll-Like 9/metabolismo , Masculino , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Nylons/química , Nylons/farmacologia , Apoptose/efeitos dos fármacos , CamundongosRESUMO
The rapid and accurate identification of rail surface defects is critical to the maintenance and operational safety of the rail. For the problems of large-scale differences in rail surface defects and many small-scale defects, this paper proposes a rail surface defect detection algorithm, RSDNet (Rail Surface Defect Detection Net), with YOLOv8n as the baseline model. Firstly, the CDConv (Cascade Dilated Convolution) module is designed to realize multi-scale convolution by cascading the cavity convolution with different cavity rates. The CDConv is embedded into the backbone network to gather earlier defect local characteristics and contextual data. Secondly, the feature fusion method of Head is optimized based on BiFPN (Bi-directional Feature Pyramids Network) to fuse more layers of feature information and improve the utilization of original information. Finally, the EMA (Efficient Multi-Scale Attention) attention module is introduced to enhance the network's attention to defect information. The experiments are conducted on the RSDDs dataset, and the experimental results show that the RSDNet algorithm achieves a mAP of 95.4% for rail surface defect detection, which is 4.6% higher than the original YOLOv8n. This study provides an effective technical means for rail surface defect detection that has certain engineering applications.
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CRISPR mutagenesis screens conducted with SpCas9 and other nucleases have identified certain cis-regulatory elements and genetic variants but at a limited resolution due to the absence of protospacer adjacent motif (PAM) sequences. Here, leveraging the broad targeting scope of the near-PAMless SpRY variant, we have demonstrated that saturated SpRY mutagenesis and base editing screens can faithfully identify functional regulatory elements and essential genetic variants for target gene expression at single-base resolution. We further extended this methodology to investigate a genome-wide association study (GWAS) locus at 10q22.1 associated with a red blood cell trait, where we identified potential enhancers regulating HK1 gene expression, despite not all of these enhancers exhibiting typical chromatin signatures. More importantly, our saturated base editing screens pinpoint multiple causal variants within this locus that would otherwise be missed by Bayesian statistical fine-mapping. Our approach is generally applicable to functional interrogation of all non-coding genomic elements while complementing other high-coverage CRISPR screens.
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Sistemas CRISPR-Cas , Estudo de Associação Genômica Ampla , Humanos , Estudo de Associação Genômica Ampla/métodos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Mutagênese , Elementos Facilitadores Genéticos/genéticaRESUMO
2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.
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Retardadores de Chama , Melatonina , Mitocôndrias , Oócitos , Animais , Melatonina/farmacologia , Camundongos , Oócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Feminino , Retardadores de Chama/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Organofosfatos/toxicidade , Dano ao DNA/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Compostos Organofosforados/toxicidadeRESUMO
Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.
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Histona Desmetilases com o Domínio Jumonji , Transtornos do Humor , Neuroglia , Condicionamento Físico Animal , Animais , Feminino , Masculino , Camundongos , Encéfalo/metabolismo , Encéfalo/imunologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Epigênese Genética , Inflamação/metabolismo , Inflamação/imunologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Camundongos Endogâmicos C57BL , Transtornos do Humor/metabolismo , Neuroglia/metabolismo , Neuroglia/imunologia , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/metabolismo , Plasticidade Neuronal/fisiologia , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Córtex Pré-Frontal/metabolismoRESUMO
Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND. Optogenetics in the DTT brain region was conducted using upconversion nanoparticles (UCNPs) with the ability to convert 808 nm near-infrared light to visible wavelengths, which triggered the activation of excitatory neurons with minimal damage in the DTT brain region, thus improving cognitive impairment symptoms in the PND model. Moreover, this noninvasive intervention to modulate E-I imbalance showed a positive influence on mouse behavior in the Morris water maze test, which demonstrates that UCNP-mediated optogenetics is a promising tool for the treatment of neurological imbalance disorders.
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Nanopartículas , Optogenética , Animais , Optogenética/métodos , Camundongos , Nanopartículas/química , Masculino , Aprendizagem em Labirinto , Complicações Cognitivas Pós-Operatórias/etiologia , Camundongos Endogâmicos C57BL , Neurônios , Fraturas da Tíbia/cirurgia , Raios InfravermelhosRESUMO
Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.
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Mononucleotídeo de Nicotinamida , Fosfatos , Tritolil Fosfatos , Feminino , Camundongos , Animais , Mononucleotídeo de Nicotinamida/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Fosfatos/metabolismo , Oócitos , Citoesqueleto , Mitocôndrias , Espécies Reativas de Oxigênio/metabolismo , MamíferosRESUMO
Mapping of expression quantitative trait loci (eQTLs) and other molecular QTLs can help characterize the modes of action of disease-associated genetic variants. However, current eQTL databases present data from bulk RNA-seq approaches, which cannot shed light on the cell type- and environment-specific regulation of disease-associated genetic variants. Here, we introduce our Single-cell eQTL Interactive Database which collects single-cell eQTL (sc-eQTL) datasets and provides online visualization of sc-eQTLs across different cell types in a user-friendly manner. Although sc-eQTL mapping is still in its early stage, our database curates the most comprehensive summary statistics of sc-eQTLs published to date. sc-eQTL studies have revolutionized our understanding of gene regulation in specific cellular contexts, and we anticipate that our database will further accelerate the research of functional genomics. Database URL: http://www.sqraolab.com/scqtl.
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Regulação da Expressão Gênica , Locos de Características Quantitativas , Humanos , Locos de Características Quantitativas/genética , RNA-Seq , Genômica , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Impaired angiogenesis, bacterial infection, persistent severe pain, exacerbated inflammation, and oxidative stress injury are intractable problems in the treatment of chronic diabetic ulcer wounds. A strategy that effectively targets all these issues has proven challenging. Herein, an in-situ sprayable nanoparticle-gel composite comprising platinum clusters (Pt) loaded-mesoporous polydopamine (MPDA) nanoparticle and QX-314-loaded fibrin gel (Pt@MPDA/QX314@Fibrin) was developed for diabetic wound analgesia and therapy. The composite shows good local analgesic effect of QX-314 mediated by near-infrared light (NIR) activation of transient receptor potential vanilloid 1 (TRPV1) channel, as well as multifunctional therapeutic effects of rapid hemostasis, anti-inflammation, antioxidation, and antibacterial properties that benefit the fast-healing of diabetic wounds. Furthermore, it demonstrates that the composite, with good biodegradability and biosafety, significantly relieved wound pain by inhibiting the expression of c-Fos in the dorsal root ganglion and the activation of glial cells in the spinal cord dorsal horn. Consequently, our designed sprayable Pt@MPDA/QX314@Fibrin composite with good biocompatibility, NIR activation of TRPV1 channel-mediated QX-314 local wound analgesia and comprehensive treatments, is promising for chronic diabetic wound therapy.
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Diabetes Mellitus , Compostos de Diazônio , Lidocaína/análogos & derivados , Nanocompostos , Piridinas , Ratos , Animais , Dor , Analgésicos/uso terapêutico , Nanocompostos/uso terapêutico , Fibrina , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.
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Fabaceae , Glucosídeos , Glucosídeos/farmacologia , Estrutura Molecular , Floroglucinol/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Espectroscopia de Ressonância Magnética , Fabaceae/química , Óxido NítricoRESUMO
Five new sesquiterpenoids (1-5), elephantmollides A-E, along with four known compounds (6-9), were isolated from the whole plants of E. mollis. Their planar structures were elucidated using the spectroscopic methods, including HRESIMS, IR, UV, and NMR (1H, 13C, DEPT, HSQC, HMBC, 1H-1H COSY). The relative configurations of them were partially deduced by the NOESY experiment, and the absolute configurations were assigned by comparing the calculated electronic circular dichroism (ECD) results with the experimental data. In addition, cytotoxic activities of 1-9 against HepG2 cells ware tested, and compounds 1-9 exhibited cytotoxic activities with IC50 values ranging from 6.7 to 25.8 µM.
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Fifteen undescribed lindenane-type sesquiterpenoid dimers, designated chloranholides F-T (1-15), together with twenty-five known analogs (16-40), were isolated from the whole plants of Chloranthus holostegius. The isolate structures were elucidated by analysis of spectroscopic data and chemical methods, and their absolute configurations were determined by X-ray crystallography and electronic circular dichroism spectra. In anti-neuroinflammatory assays, all isolates were evaluated by examination of their inhibitory effect on nitric oxide (NO) in LPS-stimulated BV-2 cells, and the results showed that 21-24, 26, 30, 32 and 36 significantly inhibited the production of the inflammatory mediator NO, with IC50 values ranging from 3.18 to 11.46 µM, which was better than that of quercetin. Structure-activity relationship analysis revealed that two essential functional groups played an indispensable role in the anti-inflammatory effects. Moreover, 22 and 24 inhibited the LPS-induced upregulation of iNOS and COX-2 enzymes in BV-2 microglia at the protein level.
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Magnoliopsida , Sesquiterpenos , Microglia/metabolismo , Lipopolissacarídeos/farmacologia , Magnoliopsida/química , Relação Estrutura-Atividade , Sesquiterpenos/química , Óxido Nítrico , Estrutura MolecularRESUMO
BACKGROUND: Peripheral nerve damage causes neuroinflammation, which plays a critical role in establishing and maintaining neuropathic pain (NeP). The mechanisms contributing to neuroinflammation remain poorly elucidated, and pharmacological strategies for NeP are limited. Thus, in this study, we planned to explore the possible link between astrocyte senescence and NeP disorders following chronic sciatic nerve injury. METHODS: An NeP animal model was established by inducing chronic constrictive injury (CCI) to the sciatic nerve in adult rats. A senolytic drug combination of dasatinib and quercetin was gavaged daily from the first postoperative day until the end of the study. Paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PTWL) were evaluated to assess behaviors in response to pain in the experimental rats. Senescence-associated ß-galactosidase staining, western blot analysis, and immunofluorescence were applied to examine the levels of proinflammatory factors and severity of the senescence-like response in the spinal cord. Lipopolysaccharide (LPS) was administered to induce senescence of spinal astrocytes in primary cultures in vitro, to explore the potential impacts of senescence on the secretion of proinflammatory factors. Furthermore, single-cell RNA sequencing (scRNA-seq) was conducted to identify senescence-related molecular responses in spinal astrocytes under neuropathic pain. RESULTS: Following sciatic nerve CCI, rats exhibited reduced PMWT and PTWL, increased levels of spinal proinflammatory factors, and an enhanced degree of senescence in spinal astrocytes. Treatment with dasatinib and quercetin effectively attenuated spinal neuroinflammation and mitigated the hypersensitivities of the rats subjected to sciatic nerve CCI. Mechanistically, the dasatinib-quercetin combination reversed senescence in LPS-stimulated primary cultured astrocytes and decreased the levels of proinflammatory factors. The scRNA-seq data revealed four potential senescence-related genes in the spinal astrocyte population, and the expression of clusterin (CLU) protein was validated via in vitro experiments. CONCLUSION: The findings indicate the potential role of astrocyte senescence in neuroinflammation following peripheral nerve injury, and suggest that targeting CLU activation in astrocytes might provide a novel therapeutic strategy to treat NeP.
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Neuralgia , Traumatismos dos Nervos Periféricos , Ratos , Animais , Astrócitos/metabolismo , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/metabolismo , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Dasatinibe/metabolismo , Doenças Neuroinflamatórias , Lipopolissacarídeos/farmacologia , Quercetina/farmacologia , Quercetina/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/metabolismoRESUMO
Cancer immunotherapy enhances the body's immunity against tumors by mitigating immune escape. Compared with traditional chemotherapy, immunotherapy has the advantages of fewer drugs, a wider range of action and fewer side effects. B7-H7 (also known as HHLA2, B7y) is a member of the B7 family of costimulatory molecules that was discovered more than 20 years ago. B7-H7 is mostly expressed in organs such as the breast, intestine, gallbladder and placenta and is detected predominantly in monocytes/macrophages in the immune system. Its expression is upregulated after stimulation by inflammatory factors such as lipopolysaccharide and interferon-γ. B7-H7/transmembrane and immunoglobulin domain containing 2 (TMIGD2) and killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 3 (KIR3DL3)-B7-H7 are the two currently confirmed signaling pathways for B7-H7. An increasing number of studies have demonstrated that B7-H7 is widely present in a variety of human tumor tissues, especially in programmed cell death-1 (PD-L1)-negative human tumors. B7-H7 promotes tumor progression, disrupts T-cell-mediated antitumor immunity, and inhibits immune surveillance. B7-H7 also triggers tumor immune escape and is associated with clinical stage, depth of tumor infiltration, metastasis, prognosis, and survival related to different tumor types. Multiple studies have shown that B7-H7 is a promising immunotherapeutic target. Herein, review the current literature on the expression, regulation, receptors and function of B7-H7 and its regulation/function in tumors.
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Neoplasias , Humanos , Neoplasias/metabolismo , Imunoterapia , Antígeno B7-H1/metabolismo , Prognóstico , Imunoglobulinas/metabolismoRESUMO
With the development of science and technology, human-machine interaction has brought great benefits to the society. Here, we design a voice and gesture signal translator (VGST), which can translate natural actions into electrical signals and realize efficient communication in human-machine interface. By spraying silk protein on the copper of the device, the VGST can achieve improved output and a wide frequency response of 20-2000 Hz with a high sensitivity of 167 mV/dB, and the resolution of frequency detection can reach 0.1 Hz. By designing its internal structure, its resonant frequency and output voltage can be adjusted. The VGST can be used as a high-fidelity platform to effectively recover recorded music and can also be combined with machine learning algorithms to realize the function of speech recognition with a high accuracy rate of 97%. It also has good antinoise performance to recognize speech correctly even in noisy environments. Meanwhile, in gesture recognition, the triboelectric translator is able to recognize simple hand gestures and to judge the distance between hand and the VGST based on the principle of electrostatic induction. This work demonstrates that triboelectric nanogenerator (TENG) technology can have great application prospects and significant advantages in human-machine interaction and high-fidelity platforms.
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Gestos , Voz , Humanos , Fala , Algoritmos , Aprendizado de MáquinaRESUMO
Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model. However, the role of ferroptosis in inflammatory pain remains inconclusive. Therefore, we aimed to explore whether ferroptosis in the spinal cord and dorsal root ganglion contributes to complete Freund's adjuvant (CFA)-induced painful behaviors in rats. Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats. These changes included iron overload, enhanced lipid peroxidation, disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels, and abnormal morphological changes in mitochondria. Intrathecal treatment of liproxstatin-1 (a ferroptosis inhibitor) reversed these ferroptosis-related changes and alleviated mechanical and thermal hypersensitivities in CFA rats. Our study demonstrated the occurrence of ferroptosis in the spinal cord and dorsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of ferroptosis inhibitors, such as liproxstatin-1, is a potential therapeutic strategy for treating inflammatory pain.
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Circular RNAs (circRNAs) are non-protein-coding RNAs that have a circular structure and do not possess a 5` cap or 3` poly-A tail. Their structure is more stable than that of linear RNAs, and they are difficult to deform via hydrolysis. Advancements in measurement technology such as RNA sequencing have enabled the detection of circRNAs in various eukaryotes in both in vitro and in vivo studies. The main function of circRNAs involves sponging of microRNAs (MiRNAs) and interaction with proteins associated with physiological and pathological processes, while some circRNAs are involved in translation. circRNAs act as tumor suppressors or oncogenes during the development of many tumors and are emerging as new diagnostic and prognostic biomarkers. They also affect resistance to certain chemotherapy drugs such as imatinib. The objective of this review is to investigate the expression and clinical significance of circRNAs in hematological malignancies. We will also explore the effect of circRNAs on proliferation and apoptosis in hematological malignancy cells and their possible use as biomarkers or targets to determine prognoses. The current literature indicates that circRNAs may provide new therapeutic strategies for patients with hematologic malignancies.
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Background: Being the S-enantiomer of racemic ketamine, esketamine is found to be effective for sedation, analgesia, and treating depression. However, there is no comprehensive bibliometric analysis about esketamine research. In this study, we aimed to determine the scientific output and emerging topics related to esketamine. Methods: Esketamine-related articles and reviews that published between 2000 and 2020 were obtained from the Web of Science Core Collection database, using key word search of "esketamine" "esketamine hydrochloride", "s-ketamine", "S(+)-ketamine", "(S)-ketamine", or "(-)-ketamine". Various bibliographic elements were collected, including the annual number of publications, citation frequency, countries/regions, institutions, authors, journals, and keywords. Two sorts of scientometric software, namely VOS viewer and CiteSpace, were used to conduct bibliometric and knowledge-map analyses. Results: A total of 683 publications were included in the current study. We found the number of publications in esketamine research field had increased annually since 2016. The United States was the leader in this field, with the highest publications number (162, 23.72%), total citations (3504/9713, 36.08%) and H-index (40). The most productive institution was Chiba University in Japan, and esketamine-related papers were mainly published in the journal Anesthesia & Analgesia. The keyword co-occurrence analysis showed that keywords relevant to depression were the most frequent. Moreover, all identified keywords could be divided into four clusters, with the research focus gradually shifting from cluster of "anesthesia and analgesia detection" to "depression treatment effect.". Conclusion: The past two decades have shown a marked increase in esketamine research. The United States maintained a top position worldwide, making the most significant contributions in the field of esketamine research. The contributions and collaborations of Asian countries have continuously increased and is a strong area of growth as well as development in recent years. Additionally, the emerging hotspots of esketamine research concentrate on clarifying its depression treatment effect.