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Objective: This study aimed to explore the global and future research trends in acupuncture interventions for stroke between 2000 and 2022 using bibliometric analysis. Method: A bibliometric analysis of literature from 2000 to 2022 in the Web of Science Core Collection was conducted in this study. The analysis utilized CiteSpace, VOSviewer, and Scimago Graphica software to identify the major contributors to publications, including authors, countries, institutions, journals, references, and keywords. Results: The bibliometric analysis yielded a total of 860 publications. There was a gradual increase in the number of publications over the study period. China published the most articles. Evidence-Based Complementary and Alternative Medicine was the journal with the greatest number of publications. The most frequently used keywords were "acupuncture," "stroke," and "electroacupuncture." Conclusion: These analysis uncovers the research trends in acupuncture for stroke spanning 2000 to 2022 and points to prospective research frontiers. This study provides a deeper and more thorough understanding of the connotations of acupuncture for stroke and guidance and support for future research in this field.
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The exploitation of hierarchical carbon nanocages with superior light-to-heat conversion efficiency, together with their distinct structural, morphological, and electronic properties, in photothermal applications could provide effective solutions to long-standing challenges in diverse areas. Here, we demonstrate the discovery of pristine and nitrogen-doped hierarchical carbon nanocages as superior supports for highly loaded, small-sized Ru particles toward enhanced photothermal CO2 catalysis. A record CO production rate of 3.1 mol·gRu-1·h-1 with above 90% selectivity in flow reactors was reached for hierarchical nitrogen-doped carbon-nanocage-supported Ru clusters under 2.4 W·cm-2 illumination without external heating. Detailed studies reveal that the enhanced performance originates from the strong broadband sunlight absorption and efficient light-to-heat conversion of nanocage supports as well as the excellent intrinsic catalytic reactivity of sub-2 nm Ru particles. Our study reveals the great potential of hierarchical carbon nanocages in photothermal catalysis to reduce the fossil fuel consumption of various industrial chemical processes and stimulates interest in their exploitation for other demanding photothermal applications.
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The chemical deconstruction of polyolefins to fuels, lubricants, and waxes offers a promising strategy for mitigating their accumulation in landfills and the environment. Yet, achieving true recyclability of polyolefins into C2-C4 monomers with high yields, low energy demand, and low carbon dioxide emissions under realistic polymer-to-catalyst ratios remains elusive. Here, we demonstrate a single-step electrified approach utilizing Rapid Joule Heating over an H-ZSM-5 catalyst to efficiently deconstruct polyolefin plastic waste into light olefins (C2-C4) in milliseconds, with high productivity at much higher polymer-to-catalyst ratio than prior work. The catalyst is essential in producing a narrow distribution of light olefins. Pulsed operation and steam co-feeding enable highly selective deconstruction (product fraction of >90% towards C2-C4 hydrocarbons) with minimal catalyst deactivation compared to Continuous Joule Heating. This laboratory-scale approach demonstrates effective deconstruction of real-life waste materials, resilience to additives and impurities, and versatility for circular polyolefin plastic waste management.
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In the contemporary realm of athletic training, integrating technology is a pivotal determinant for augmenting athlete performance and refining training outcomes. The amalgamation of multi-target visual modeling with sensor technology imparts an enriched stratum of sports training data. Subsequently, the sensor scale-space transformation accentuates the comprehensive apprehension of data across diverse scales and angles. Hence, within this manuscript, addressing the multi-target tracking intricacies during sports training and competition, we posit a framework that amalgamates the shortest path elucidated by the K shortest paths (KSP) methodology with the pose information emanating from the Alphapose network. This framework recognizes the athlete's shortest path through a convolutional neural network and KSP, followed by the amalgamation of these divergent data sources. The fusion unfolds by incorporating the athlete's pose information grounded in Alphapose, culminating in a comprehensive integration of the two data streams. Consequently, synthesizing alpha-derived athlete information precipitates the ultimate amalgamation of the two information streams. The accomplished fusion, premised on Alphapose, forms the bedrock for multi-target tracking, culminating in a feature-rich synthesis. Empirical results reveal that after integrating these information streams, the Multiple Object Tracking Accuracy (MOTA) index and Global Multiple Object Tracking Accuracy (GMOTA) index surpass those of the solitary information tracking methods, thereby furnishing a technical underpinning and a foundation for information fusion within prospective sports training analysis systems.
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Anxiety and depression are the most common mental health disorders worldwide, each affecting around 30% stroke survivors. These complications not only affect the functional recovery and quality of life in stroke patients, but also are distressing for caregivers. However, effective treatments are still lacking. Enriched environment (EE), characterized with novel and multi-dimensional stimulation, has been reported to exert therapeutic effects on physical and cognitive function. In addition, EE also had potential positive effects on emotional disorders after ischemic stroke; however, the underling mechanisms have not been well elucidated. This study aimed to explore the effectiveness of EE on emotional disorders after cerebral ischemia and its underling mechanism. Sensorimotor cortical infarction was induced by photothrombosis with stable infarct location and volume, resulting in motor dysfunction, anxiety and depression-like behaviors in mice, with decreased ALFF and ReHo values and decreased c-fos expression in the infarction area and adjacent regions. Seven days' EE treatment significantly improved motor function of contralateral forelimb and exhibited anxiolytic and antidepressant effects in infarcted mice. Compared to the mice housing in a standard environment, those subjected to acute EE stimulation had significantly increased ALFF and ReHo values in the bilateral somatosensory cortex (S1, S2), dorsal dentate gyrus (dDG), dorsal CA1 of hippocampus (dCA1), lateral habenular nucleus (LHb), periaqueductal gray (PAG), ipsilateral primary motor cortex (M1), retrosplenial cortex (RSC), parietal association cortex (PtA), dorsal CA3 of hippocampus (dCA3), claustrum (Cl), ventral pallidum (VP), amygdala (Amy), and contralateral auditory cortex (Au). Some of, but not all, the ipsilateral brain regions mentioned above showed accompanying increases in c-fos expression with the most significant changes in the dDG. The number of FosB positive cells in the dDG, decreased in infarcted mice, was significantly increased after chronic EE treatment. Chemogenetic activation of dDG neurons reduced anxiety and depressive-like behaviors in infarcted mice, while neuronal inhibition resulted in void of the anxiolytic and antidepressant effects of EE. Altogether, these findings indicated that dDG neurons may mediate EE-triggered anxiolytic and antidepressant effects in cortical infarcted mice.
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Ansiedad , Infarto Cerebral , Giro Dentado , Depresión , Ratones Endogámicos C57BL , Animales , Ratones , Giro Dentado/efectos de los fármacos , Giro Dentado/metabolismo , Masculino , Ansiedad/etiología , Ansiedad/terapia , Depresión/etiología , Depresión/terapia , Ambiente , Imagen por Resonancia MagnéticaRESUMEN
Neurovascular decoupling plays a significant role in dysfunction following an ischemic stroke. This study aimed to explore the effect of low- and high-frequency repetitive transcranial magnetic stimulation on neurovascular remodeling after ischemic stroke. To achieve this goal, we compared functional hyperemia, cerebral blood flow regulatory factors, and neurochemical transmitters in the peri-infract cortex 21 days after a photothrombotic stroke. Our findings revealed that low- and high-frequency repetitive transcranial magnetic stimulation increased the real-time cerebral blood flow in healthy mice and improved neurobehavioral outcomes after stroke. Furthermore, high-frequency (5-Hz) repetitive transcranial magnetic stimulation revealed stronger functional hyperemia recovery and increased the levels of post-synaptic density 95, neuronal nitric oxide synthase, phosphorylated-endothelial nitric oxide synthase, and vascular endothelial growth factor in the peri-infract cortex compared with low-frequency (1-Hz) repetitive transcranial magnetic stimulation. The magnetic resonance spectroscopy data showed that low- and high-frequency repetitive transcranial magnetic stimulation reduced neuronal injury and maintained excitation/inhibition balance. However, 5-Hz repetitive transcranial magnetic stimulation showed more significant regulation of excitatory and inhibitory neurotransmitters after stroke than 1-Hz repetitive transcranial magnetic stimulation. These results indicated that high-frequency repetitive transcranial magnetic stimulation could more effectively promote neurovascular remodeling after stroke, and specific repetitive transcranial magnetic stimulation frequencies might be used to selectively regulate the neurovascular unit.
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Hiperemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Ratones , Estimulación Magnética Transcraneal/métodos , Factor A de Crecimiento Endotelial Vascular , Resultado del TratamientoRESUMEN
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy in post-stroke motor recovery. However, the underlying mechanisms of rTMS regulates long-lasting changes with synaptic transmission and glutamate receptors function (including AMPARs or NMDARs) remains unclear. METHODS: Mice were received 10-Hz rTMS treatment once daily on the third day after photothrombotic (PT) stroke for 18 days. Motor behaviors and the Western blot were used to evaluate the therapeutic efficacy of 10-Hz rTMS in the mice with PT model. Moreover, we used wild-type (WT) and NEX-α3-/- mice to further explore the 10-Hz rTMS effect. RESULTS: We found that 10-Hz rTMS improved the post-stroke motor performance in the PT mice. Moreover, the levels of AMPAR, vGlut1, and integrin α3 in the peri-infarct were significantly increased in the rTMS group. In contrast, 10-Hz rTMS did not induce these aforementioned effects in NEX-α3-/- mice. The amplitude of AMPAR-mediated miniature excitatory postsynaptic currents (EPSCs) and evoked EPSCs was increased in the WT + rTMS group, but did not change in NEX-α3-/- mice with rTMS. CONCLUSIONS: In this study, 10-Hz rTMS improved the glutamatergic synaptic transmission in the peri-infract cortex through effects on integrin α3 and AMPARs, which resulted in motor function recovery after stroke.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Animales , Ratones , Humanos , Estimulación Magnética Transcraneal/métodos , Integrina alfa3 , Resultado del Tratamiento , Accidente Cerebrovascular/terapia , Transmisión Sináptica , Isquemia , Rehabilitación de Accidente Cerebrovascular/métodosRESUMEN
Introduction: Circular RNA (circRNAs) are a type of non-coding RNA (ncRNAs) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic kidney disease (DKD), owing to their stability and enrichment in exosomes. However, the role of circRNAs in exosomes of tubular epithelial cells in DKD development has not been fully elucidated. Methods: In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. The small interfering RNAs (siRNA) and plasmid overexpression were used to validate functions of differentially expressed circRNAs. Results: We found that exosome concentration was higher in HG-stimulated HK-2 cells than in controls. A total of 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of the HG group. In parallel with the microarray data, the qPCR results showed that the expression of circ_0009885, circ_0043753, and circ_0011760 increased, and the expression of circ_0032872, circ_0004716, and circ_0009445 decreased in the HG group. Rescue experiments showed that the effects of high glucose on regulation of CCL2, IL6, fibronetin, n cadherin, e cadherin and epcam expression can be reversed by inhibiting or overexpressing these circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses indicated that circRNA parental genes are associated with glucose metabolism, lipid metabolism, and inflammatory processes, which are important in DKD development. Further analysis of circRNA/miRNA interactions indicated that 152 differentially expressed circRNAs with fold change (FC) ≥1.5 could be paired with 43 differentially expressed miRNAs, which are associated with diabetes or DKD. Discussion: Our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers, and may play a critical role in the progression of DKD.
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Homeodomain-interacting protein kinases (Hipks) regulate cell proliferation, apoptosis, and tissue development. Overexpression of Hipk in Drosophila causes tumorigenic phenotypes in larval imaginal discs. We find that depletion of Salt-inducible kinases Sik2 or Sik3 can suppress Hipk-induced overgrowth. Furthermore, co-expression of constitutively active forms of Sik2 or Sik3 with Hipk caused significant tissue hyperplasia and tissue distortion, indicating that both Sik2 and Sik3 can synergize with Hipk to promote tumorous phenotypes, accompanied by elevated dMyc, Armadillo/ß-catenin, and the Yorkie target gene expanded. Larvae expressing these hyperplastic growths also display an extended larval phase, characteristic of other Drosophila tumour models. Examination of total protein levels from fly tissues showed that Hipk proteins were reduced when Siks were depleted through RNAi, suggesting that Siks may regulate Hipk protein stability and/or activity. Conversely, expression of constitutively active Siks with Hipk leads to increased Hipk protein levels. Furthermore, Hipk can interact with Sik2 and Sik3 by co-immunoprecipitation. Co-expression of both proteins leads to a mobility shift of Hipk protein, suggesting it is post-translationally modified. In summary, our research demonstrates a novel function of Siks in synergizing with Hipk to promote tumour growth.
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Nonoxidative propane dehydrogenation (PDH) produces on-site propylene for value-added chemicals. While commercial, its modest selectivity and catalyst deactivation hamper the process efficiency and limit operation to lower temperatures. We demonstrate PDH in a microwave (MW)-heated reactor over PtSn/SiO2 catalyst pellets loaded in a SiC monolith acting as MW susceptor and a heat distributor while ensuring comparable conditions with conventional reactors. Time-on-stream experiments show active and stable operation at 500°C without hydrogen addition. Upon increasing temperature or feed partial pressure at high space velocity, catalysts under MWs show resistance in coking and sintering, high activity, and selectivity, starkly contrasting conventional reactors whose catalyst undergoes deactivation. Mechanistic differences in coke formation are exposed. Gas-solid temperature gradients are computationally investigated, and nanoscale temperature inhomogeneities are proposed to rationalize the different performances of the heating modes. The approach highlights the great potential of electrification of endothermic catalytic reactions.
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With time, the number of samples in clinical laboratories from therapeutic drug monitoring has increased. Existing analytical methods for blood cyclosporin A (CSA) monitoring, such as high-performance liquid chromatography (HPLC) and immunoassays, have limitations including cross-reactivity, time consumption, and the complicated procedures involved. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has long been considered the reference standard owing to its high accuracy, specificity, and sensitivity. However, large numbers of blood samples, multi-step preparation procedures, and longer analytical times (2.5-20 min) are required as a consequence of the different technical strategies, to ensure good analytical performance and routine quality assurance. A stable, reliable, and high throughput detection method will save personnel time and reduce laboratory costs. Therefore, a high throughput and simple LC-MS/MS method was developed and validated for the detection of whole-blood CSA with CSA-d12 as the internal standard in the present study. Whole blood samples were prepared through a modified one-step protein precipitation method. A C18 column (50x2.1 mm, 2.7 µm) with a mobile phase flow rate of 0.5 ml/min was used for chromatographic separation with a total running time of 4.3 min to avoid the matrix effect. To protect the mass spectrometer, only part of the sample after LC separation was allowed to enter the mass spectrum, using two HPLC systems coupled to one mass spectrometry. In this way, throughput was improved with detection of two samples possible within 4.3 min using a shorter analytical time for each sample of 2.15 min. This modified LC-MS/MS method showed excellent analytical performance and demonstrated less matrix effect and a wide linear range. The design of multi-LC systems coupled with one mass spectrometry may play a notable role in the improvement of daily detection throughput, speeding up LC-MS/MS, and allowing it to be an integral part of continuous diagnostics in the near future.
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We employ a nonthermal, He/O2 atmospheric plasma as an efficient surface functionalization method of activated carbons. We show that plasma treatment rapidly increases the surface oxygen content from 4.1 to 23.4% on a polymer-based spherical activated carbon in 10 min. Plasma treatment is 3 orders of magnitude faster than acidic oxidation and introduces a diverse range of carbonyl (CâO) and carboxyl (O-CâO) functionalities that were not found with acidic oxidation. The increased oxygen functionalities reduce the particle size of a high 20 wt % loading Cu catalyst by >44% and suppress the formation of large agglomerates. Increased metal dispersion exposes additional active sites and improves the yield of hydrodeoxygenation of 5-hydroxymethyl furfural to 2,5-dimethyl furan, an essential compound for biofuel replacement, by 47%. Surface functionalization via plasma can advance catalysis synthesis while being rapid and sustainable.
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Repetitive TMS has been used as an alternative treatment for various neurological disorders. However, most TMS mechanism studies in rodents have been based on the whole brain stimulation, the lack of rodent-specific focal TMS coils restricts the proper translation of human TMS protocols to animal models. In this study, we designed a new shielding device, which was made of high magnetic permeability material, to enhance the spatial focus of animal-use TMS coils. With the finite element method, we analyzed the electromagnetic field of the coil with and without the shielding device. Furthermore, to assess the shielding effect in rodents, we compared the c-fos expression, the ALFF and ReHo values in different groups following a 15 min 5 Hz rTMS paradigm. We found that a smaller focality with an identical core stimulation intensity was achieved in the shielding device. The 1 T magnetic field was reduced from 19.1 mm to 13 mm in diameter, and 7.5 to 5.6 mm in depth. However, the core magnetic field over 1.5 T was almost the same. Meanwhile, the area of electric field was reduced from 4.68 cm2 to 4.19 cm2, and 3.8 mm to 2.6 mm in depth. Similar to this biomimetic data, the c-fos expression, the ALFF and ReHo values showed more limited cortex activation with the use of the shielding device. However, compared to the rTMS group without the shielding application, more subcortical regions, like the striatum (CPu), the hippocampus, the thalamus, and the hypothalamus were also activated in the shielding group. This indicated that more deep stimulation may be achieved by the shielding device. Generally, compared with the commercial rodents' TMS coil (15 mm in diameter), TMS coils with the shielding device achieved a better focality (~6 mm in diameter) by reducing at least 30% of the magnetic and electric field. This shielding device may provide a useful tool for further TMS studies in rodents, especially for more specific brain area stimulation.
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Dopamine (DA) plays an essential role in dopaminergic neuronal behavior and disease. However, current detection methods for discriminating the secretion of DA are hampered by the limitations of the requirement for bulky instrumentation and non-intuitive signals. Herein, we have controllably and proportionately integrated molybdenum disulfide (MoS2) with titanium dioxide (TiO2) to prepare MoS2@TiO2 nanocomposites (MoS2@TiO2 NCs) via a facile synthesis method. MoS2@TiO2 NCs with a certain reactant mass ratio have shown a significant enhancement in peroxidase-like activity with superiority of the nanocomposite structure compared to single MoS2 or natural enzyme. The method for catalyzing the decomposition of H2O2 by MoS2@TiO2 NCs and competition for hydroxyl radicals (ËOH) between the chromogenic agent and DA enable a sensitive, specific, and colorimetric DA analysis with a low detection limit of 0.194 µM and a wide linear detection range (0.8 to 100 µM). Because of the favorable detection performance, we were encouraged to explore and finally realize the visual detection of cellular DA secretion that is stimulated in a High-K+ neurocyte environment. Collectively, this method will provide a promising strategy for basic research in neuroscience with its portable, sensitive, and naked-eye detectable performance.
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Dopamina , Nanocompuestos , Molibdeno/química , Peróxido de Hidrógeno/química , Nanocompuestos/químicaRESUMEN
Stroke seriously affects human health. Many studies have shown that enriched environment (EE) can promote functional recovery after stroke, but the intrinsic mechanisms remain unclear. In order to study the internal mechanisms of EE involved in functional recovery after ischemic stroke and which mechanism plays a leading role in the recovery of limb function after cerebral infarction, key proteins potentially involved in neuronal protection and synaptic remodeling in the ischemic penumbra have been investigated. In this study, adult C57BL/6 mice after permanent middle cerebral artery occlusion (pMCAO) were assigned to the EE and standard housing (SH) groups 3 days after operation. The EE house was spacious that contained a large variety of small toys; the SH was a normal sized cage. Sham-operated mice without artery occlusion were housed under standard conditions and were fed a normal diet. On days 3, 7, 14, and 21, postoperative motor functional recovery was tested using the modified neurological severity score (mNSS) and the Rotarod test. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) was examined by western blotting and immunofluorescence staining. The motor functional recovery (based on the mNSS and Rotarod test 3, 7, 14, and 21 days post operation) of mice in the EE group improved significantly compared to the SH group. The expression of GAP-43 and SYN and the ratio of Bcl-2/Bax were all upregulated in the EE group compared to the SH group. In addition, we also explored the relationship between neuronal protection and synaptic remodeling in the EE-mediated recovery of limb function after cerebral infarction by correlation analysis. Correlation analysis showed that compared with the increase of Bcl-2/Bax ratio, the increased expression of GAP-43 and SYN was more closely related to the recovery of limb function in ischemic mice. These data support the hypothesis that EE can promote the process of improvement of limb dysfunction induced by ischemic stroke, and this behavior restoration may, via promoting neuroprotection in the ischemic penumbra, be dependent on the regulation of the expression of GAP-43, SYN, Bcl-2, and Bax. A limitation of the study was that we only observed several representative key indicators of synaptic remodeling and neuronal apoptosis, without an in-depth study of the potential mechanisms involved.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Ratones , Animales , Neuroprotección , Proteína X Asociada a bcl-2 , Proteína GAP-43 , Ratones Endogámicos C57BL , Infarto de la Arteria Cerebral Media , Modelos Animales de EnfermedadRESUMEN
The current study investigated the effects of intermittent feeding (IF) and fasting strategies at different times post-hatch on muscle growth and white striping (WS) breast development. In the first trial, 32 one-day-old Abor Acre broilers were fed ad libitum (AL) for 3 d post-hatch and then randomly allotted into 4 feeding strategies including AL, 1h-IF group (1 h IF, 4 times feeding/d, 1 h each time), 1.5h-IF (1.5 h IF, 4 times feeding/d, 1.5 h each time), and fasting (1d acute fasting, 6 d free access to feed) groups and fed for 7 d. Although angiogenic genes including VEGFA, VEGFR1, and VEGFR2, and myogenic genes including MYOG and MYOD were upregulated (P < 0.05), the breast muscle satellite cell (SC) number and PAX7, MYF5 expression were decreased by the IF strategies (P < 0.05). One-day fasting at 6 d of age also upregulated angiogenic genes and MYOD expression (P < 0.05), downregulated MYF5 expression (P < 0.05), but did not change SC number (P > 0.05). In the second trial, 384 one-day-old birds were fed AL for 1 wk and then randomly allotted to the above 4 feeding strategies starting at 8 d of age until 42 d of age. Similarly, IF and fasting strategies upregulated the expression of angiogenic and myogenic genes (P < 0.05). Both 1h-IF and 1.5h-IF increased breast muscle SC number (P < 0.05). At slaughter, breast muscle fiber diameter of 1.5h-IF was smaller but the SC number was larger than that of the birds fed AL (P < 0.05). The IF and fasting strategies prevented WS development, and reduced breast WS scores and triglyceride content (P < 0.05) without changing the body weight (P > 0.05). Fasting and 1h-IF reduced the expression of adipogenic genes ZNF423 and PDGFRα (P < 0.05). Moreover, IF and fasting strategies reduced fibrosis in breast muscle and reduced skeletal muscle-specific E3 ubiquitin ligases (TRIM63 and MAFBX) (P < 0.05). Fasting significantly reduced CASPASE-3 in breast muscle (P < 0.05). In conclusion, IF starting in the first week decreases SC number. Compared to AL, IF or fasting promotes muscular angiogenesis, increases SC number, prevents muscle degeneration, and prevents the development of WS without impairing the growth performance of broiler chickens.
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Background: Glioma is a highly aggressive brain cancer with a poor prognosis. Necroptosis is a form of programmed cell death occurring during tumor development and in immune microenvironments. The prognostic value of necroptosis in glioma is unclear. This study aimed to develop a prognostic glioma model based on necroptosis. Methods: A necroptosis-related risk model was constructed by Cox regression analysis based on The Cancer Genome Atlas (TCGA) training set, validated in two Chinese Glioma Genome Atlas (CGGA) validation sets. We explored the differences in immune infiltration and immune checkpoint genes between low and high risk groups and constructed a nomogram. Moreover, we compiled a third validation cohort including 43 glioma patients. The expression of necroptosis-related genes was verified in matched tissues using immunochemical staining in the third cohort, and we analyzed their relationship to clinicopathological features. Results: Three necroptosis-related differentially expressed genes (EZH2, LEF1, and CASP1) were selected to construct the prognostic model. Glioma patients with a high risk score in the TCGA and CGGA cohorts had significantly shorter overall survival. The necroptosis-related risk model and nomogram exhibited good predictive performance in the TCGA training set and the CGGA validation sets. Furthermore, patients in the high risk group had higher immune infiltration status and higher expression of immune checkpoint genes, which was positively correlated with poorer outcomes. In the third validation cohort, the expression levels of the three proteins encoded by EZH2, LEF1, and CASP1 in glioma tissues were significantly higher than those from paracancerous tissues. They were also closely associated with disease severity and prognosis. Conclusions: Our necroptosis-related risk model can be used to predict the prognosis of glioma patients and improve prognostic accuracy, which may provide potential therapeutic targets and a theoretical basis for treatment.
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Neoplasias Encefálicas , Glioma , Humanos , Necroptosis/genética , Glioma/patología , Pronóstico , Nomogramas , Microambiente Tumoral/genéticaRESUMEN
Background: Blindness and stroke resulting from hyaluronic acid (HA) fillers are not frequently reported complications. Reports on stroke recovery after HA injection are limited. In the current study, the recovery process, task-based functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and neurophysiological changes of a patient with monocular blindness and ipsilateral motor cortical stroke after forehead injection of HA are explored. Case-report: The study comprised a 34-year-old female patient who presented with left eye blindness and a stroke after receiving an HA injection a month before admission. The lesion was mainly limited to the left precentral gyrus, and the patient had pure arm monoparesis. For 3 weeks, the patient received conventional rehabilitation treatments and ten sessions of repetitive transcranial magnetic stimulation (rTMS) intervention. Clinical assessments, neurophysiological evaluation, task-based fMRI, and DTI examinations were conducted to assess her motor improvement and the possible neuro mechanism. Clinical rehabilitation impact: The patient's right upper limb motor function was almost completely restored after receiving rehabilitation therapy. However, the vision in her left eye did not show significant improvement. The neurophysiological evaluation showed partial recovery of the ipsilesional motor evoked potentials (MEPs). DTI results showed that the ipsilesional corticospinal tract (CST) was intact. Task-based fMRI results indicated that the activation pattern of the affected hand movement was gradually restored to normal. Conclusion: A case of good motor recovery after stroke due to HA injection with a lesion mainly restricted to the precentral gyrus but without CST damage is presented in the current study. Further studies should be conducted to explore the efficacy and the mechanisms of rehabilitation and neuromodulation approaches to motor cortical stroke.
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Background: For patients who treated with tacrolimus after kidney transplant, therapeutic drug monitoring is essential to improve their prognosis. However, previous detection methods have limitations, such as the overestimation and unacceptable bias in the immunoassays. Precision medicine has been challenged. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is recognized as the gold standard due to its accuracy and specificity, but lack of throughput and complex process limits its clinical application. Therefore, an accurate, simple and high throughput method for tacrolimus monitoring is needed for clinical practice. Methods: A modified LC-MS/MS method was introduced and validated. Whole blood samples were prepared by a one-step protein precipitation method. Chromatographic separation was achieved using a Phenomenex Kinetex 2.6 µm XB-C18 2.1 × 50 mm column with a total run time of 3.5 min to avoid matrix effect. An electrospray ionization source (ESI) was used in positive ion multiple reaction monitoring (MRM) mode for mass spectrometric detection. In order to protect the mass spectrometer, only part of the sample after LC separation was allowed to enter the mass spectrum, through a two HPLC systems coupled one mass spectrometry design. In this way, the instrument throughput is also improved and realizing the detection of 2 samples within 3.5 min and carried out a shorter analyzing time for each sample of 1.75 min. Additionally, we calculated tacrolimus-intrapatient variant (Tac-IPV) based on this modified method and assessed the prognostic value of Tac-IPV in Chinese kidney transplant patients. Results: The LC-MS/MS was modified by streamlining the procedure and increasing the throughput. The method proved to be accurate and reproducible with all performance parameters suitably meeting the clinical requirements over a calibration ranged from 0.37 to 42.90 ng/mL. Parameters such as linearity, limit of quantification (LoQ) and dilution integrity were validated with a clinical reportable range from 0.37 to 343.20 ng/mL, which was particularly useful for high drug concentrations patients (rare but very serious). Both cross-contamination and matrix effects were negligible. Clinical data of 83 patients showed that Tac-IPV was associated with poor kidney transplant outcome in Chinese (Hazard Ratio (HR) = 3.96, 4.75; 95% Cl: 1.10-14.21, 1.23-18.36; P < 0.05). Conclusions: This modified LC-MS/MS method possessed high throughput and simple sample preparation, allowing it to meet daily clinical needs. At the same time, Tac-IPV based on this modified LC-MS/MS had excellent prognostic value in kidney transplantation. These advantages have great significance for the individualized treatment of Chinese kidney transplant patients and broad application of Tac-IPV.
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Background: Enriched environment (EE) can protect the brain against damages caused by an ischemic stroke; however, the underlying mechanism remains elusive. Autophagy and mitochondria quality control are instrumental in the pathogenesis of ischemic stroke. In this study, we investigated whether and how autophagy and mitochondria quality control contribute to the protective effect of EE in the acute phase of cerebral ischemia-reperfusion injury. Methods: We exposed transient middle cerebral artery occlusion (tMCAO) mice to EE or standard condition (SC) for 7 days and then studied them for neurological deficits, autophagy and inflammation-related proteins, and mitochondrial morphology and function. Results: Compared to tMCAO mice in the SC group, those in the EE group showed fewer neurological deficits, relatively downregulated inflammation, higher LC3 expression, higher mitochondrial Parkin levels, higher mitochondrial fission factor dynamin-related protein-1 (Drp1) levels, lower p62 expression, and lower autophagy inhibitor mTOR expression. Furthermore, we found that the EE group showed a higher number of mitophagosomes and normal mitochondria, fewer mitolysosomes, and relatively increased mitochondrial membrane potential. Conclusion: These results suggested that EE enhances autophagy flux by inhibiting mTOR and enhances mitophagy flux via recruiting Drp1 and Parkin to eliminate dysfunctional mitochondria, which in turn inhibits inflammation and alleviates neurological deficits. Limitations. The specific mechanisms through which EE promotes autophagy and mitophagy and the signaling pathways that link them with inflammation need further study.