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BACKGROUND: The purpose of this study was to investigate the predictive value of the 5-factor modified frailty index (mFI-5) for postoperative mortality, delirium and pneumonia in patients over 65 years of age undergoing elective lung cancer surgery. METHODS: Data were collected from a single-center retrospective cohort study conducted in a general tertiary hospital from January 2017 to August 2019. In total, the study included 1372 elderly patients aged over 65 who underwent elective lung cancer surgery. They were divided into frail group (mFI-5, 2-5), prefrail group (mFI-5, 1) and robust group (mFI-5, 0) on the basis of mFI-5 classification. The primary outcome was postoperative 1-year all-cause mortality. Secondary outcomes were postoperative pneumonia and postoperative delirium. RESULTS: Frailty group had the highest incidence of postoperative delirium (frailty 31.2% versus prefrailty 1.6% versus robust 1.5%, p < 0.001), postoperative pneumonia (frailty 23.5% versus prefrailty 7.2% versus robust 7.7%, p < 0.001), and postoperative 1-year mortality (frailty 7.0% versus prefrailty 2.2% versus robust 1.9%. p < 0.001). Frail patients have significantly longer length of hospitalization than those in the robust group and prefrail patients (p < 0.001). Multivariate analysis showed a clear link between frailty and increased risk of postoperative delirium (aOR 2.775, 95% CI 1.776-5.417, p < 0.001), postoperative pneumonia (aOR 3.291, 95% CI 2.169-4.993, p < 0.001) and postoperative 1-year mortality (aOR 3.364, 95% CI, 1.516-7.464, p = 0.003). CONCLUSIONS: mFI-5 has potential clinical utility in predicting postoperative death, delirium and pneumonia incidence in elderly patients undergoing radical lung cancer surgery. Frailty screening of patients (mFI-5) may provide benefits in risk stratification, targeted intervention efforts, and assist physicians in clinical decision-making.
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PURPOSE: This study aims to explore the emerging trends, dynamic development, and research hotspots of clustered regularly interspaced short palindromic repeats (CRISPR) technology associated with extracellular vesicles during the past 7 years and demonstrate them by visualization. METHODS: A total of 219 records related to CRISPR technology associated with extracellular vesicles from 2015 to 2022 in the Web of Science Core Collection (WoSCC) database were collected. R language, VOSviewer, CiteSpace, and GraphpadPrism software packages were used to analyze the history of this research, the general characteristics of the literature, and keywords. Finally, the hotspots and latest trends in CRISPR technology associated with extracellular vesicles are predicted. RESULTS: A total of 219 articles were collected for this study. The production of publications about CRISPR technology associated with extracellular vesicles has increased annually. Researchers from China, the USA, and Germany made the most important contributions to this trend, while RLUK Research Libraries UK offers the largest amount of literature in this field. Shenzhen University, Nanjing Medicine University, and Peking University exhibited the closest cooperation. Additionally, active topics burst during different periods, as identified according to 317 keywords belonging to 39 disciplines. Keywords were clustered into seven research subareas, namely exosome, nanovesicles, DNA, gene editing, gene therapy, cancer therapy, and endometrial stromal cells. The alluvial map of keywords reveals that the most enduring concepts are gene therapy, nanovesicles, etc., while the emerging keywords are genome, protein delivery, plasma, etc. CONCLUSIONS: We reviewed 219 previous publications and conducted the first bibliometric study of CRISPR technology related to extracellular vesicles from 2015 to 2022. This comprehensive summary constructed a knowledge map and demonstrates the trends in this area. The current trends and potential hotpots for this topic are also identified, which will be a great help for researchers in the future.
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Exossomos , Vesículas Extracelulares , Humanos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Bibliometria , Bases de Dados FactuaisRESUMO
Colitis-associated colorectal cancer (CAC) arises due to prolonged inflammation and has distinct molecular events compared with sporadic colorectal cancer (CRC). Although inflammatory NF-κB signaling was activated by pro-inflammatory cytokines (such as TNFα) in early stages of CAC, Wnt/ß-catenin signaling later appears to function as a key regulator of CAC progression. However, the exact mechanism responsible for the cross-regulation between these 2 pathways remains unclear. Here, we found reciprocal inhibition between NF-κB and Wnt/ß-catenin signaling in CAC samples, and the Dvl2, an adaptor protein of Wnt/ß-catenin signaling, is responsible for NF-κB inhibition. Mechanistically, Dvl2 interacts with the C-terminus of tumor necrosis factor receptor 1 (TNFRI) and mediates TNFRI endocytosis, leading to NF-κB signal inhibition. In addition, increased infiltration of the pro-inflammatory cytokine interleukin-13 (IL-13) is responsible for upregulating Dvl2 expression through STAT6. Targeting STAT6 effectively decreases Dvl2 levels and restrains colony formation of cancer cells. These findings demonstrate a unique role for Dvl2 in TNFRI endocytosis, which facilitates the coordination of NF-κB and Wnt to promote CAC progression.
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Neoplasias Associadas a Colite/metabolismo , Proteínas Desgrenhadas/metabolismo , NF-kappa B/metabolismo , Proteínas Wnt/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Associadas a Colite/genética , Neoplasias Associadas a Colite/patologia , Citocinas/metabolismo , Progressão da Doença , Proteínas Desgrenhadas/genética , Endocitose , Regulação Neoplásica da Expressão Gênica , Humanos , Inflamação , Camundongos , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Lung adenocarcinoma (LUAD) is the most common type of lung cancers, which remains the leading cause of cancer-related death worldwide. Drebrin can promote cell migration and invasion with poor prognosis, but its roes in LUAD tumor progression remains unknown. We showed that the expression of Drebrin was upregulated in clinical LUAD samples. A Kaplan-Meier survival analysis showed that a high expression of Drebrin predicated poor prognosis in LUAD. In vitro, Drebrin promoted anchorage-independent growth and migration of LUAD cells. Drebrin interacted with dynamin through CT domain, and served as an adaptor to promote LUAD cell migration through inducing integrin ß1 endocytosis. Thus, this study demonstrated the critical role of Drebrin in LUAD and associated mechanism.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Neuropeptídeos , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Endocitose , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina beta1/genética , Integrina beta1/metabolismo , Neoplasias Pulmonares/patologia , Neuropeptídeos/genéticaRESUMO
The present work reports data for the mineralogical and chemical properties of anatase thin films individually doped or codoped with chromium and vanadium, fabricated by sol-gel spin coating on glass substrates and annealing at 450 °C for 2 h. X-ray photoelectron spectroscopy data indicated the presence of Ti(4+), Ti(3+), Cr(3+), and possibly Cr(4+) in the Cr-doped thin films; Ti(4+), Ti(3+), V(3+), V(4+), and possibly V(5+) in the V-doped thin films; and Ti(4+), Ti(3+), Cr(3+), Cr(4+), V(3+), V(4+), and possibly V(5+) in the codoped thin films. While the thermodynamically stable valences Ti(4+), Cr(3+), and V(5+) would be expected to have formed, the presence of the nonequilibrium valences Ti(3+), Cr(4+), V(3+), and V(4+) is considered to have resulted from intervalence charge transfer for the Cr-doped and V-doped systems but from multivalence charge transfer (MVCT) for the codoped system. The latter phenomenon, which is introduced as a new conceptual term, describes the nature of the mutual exchange of electrons during valence changes of both dopant (Cr, V) and matrix (Ti) ions during annealing. In the present case, MVCT appears to be a transient metastable condition that acts during annealing, but subsequent UV irradiation can alter its effects.
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Induction skull melting (ISM) technology could melt metals with avoiding contamination from crucible. A long-standing problem of ISM is that the low charge energy utilization and inhomogeneous fields have obstructed its application in many critical metal materials and manufacturing processes. The present work investigated the problem through the structure optimization strategy and established a numerical electromagnetic-field model to evaluate components' eddy current loss. Based on the model, the effect of crucible and inductor structure on charge energy utilization, etc. was studied. Furtherly, the charge energy utilization was increased from 27.1 to 45.89% by adjusting the system structure. Moreover, structure modifications are proposed for enhancing electromagnetic intensity and uniformity, charge soft contact and uniform heating. The work constructed a basis for framing new solutions to the problem through ISM device structure optimization.
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AIMS: General anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTADA ) to the PrL play a role in the transition from sevoflurane anesthesia to arousal. It is still uncertain whether the prelimbic cortex pyramidal neuron (PrLPyr ) and its projections to VTA (PrLPyr -VTA) are involved in anesthesia-arousal regulation. METHODS: We employed chemogenetics and optogenetics to selectively manipulate neuronal activity in the PrLPyr -VTA pathway. Electroencephalography spectra and burst-suppression ratios (BSR) were used to assess the depth of anesthesia. Furthermore, the loss or recovery of the righting reflex was monitored to indicate the induction or emergence time of general anesthesia. To elucidate the receptor mechanisms in the PrLPyr -VTA projection's impact on anesthesia and arousal, we microinjected NMDA receptor antagonists (MK-801) or AMPA receptor antagonists (NBQX) into the VTA. RESULTS: Our findings show that chemogenetic or optogenetic activation of PrLPyr neurons prolonged anesthesia induction and promoted emergence. Additionally, chemogenetic activation of the PrLPyr -VTA neural pathway delayed anesthesia induction and promoted anesthesia emergence. Likewise, optogenetic activation of the PrLPyr -VTA projections extended the induction time and facilitated emergence from sevoflurane anesthesia. Moreover, antagonizing NMDA receptors in the VTA attenuates the delayed anesthesia induction and promotes emergence caused by activating the PrLPyr -VTA projections. CONCLUSION: This study demonstrates that PrLPyr neurons and their projections to the VTA are involved in facilitating emergence from sevoflurane anesthesia, with the PrLPyr -VTA pathway exerting its effects through the activation of NMDA receptors within the VTA.
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Receptores de N-Metil-D-Aspartato , Área Tegmentar Ventral , Área Tegmentar Ventral/metabolismo , Sevoflurano/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Neurônios Dopaminérgicos/metabolismo , Células Piramidais , Anestesia Geral , Nível de AlertaRESUMO
Background: Numerous approaches have been utilized to optimize mesenchymal stem cells (MSCs) performance in treating osteoarthritis (OA), however, the constrained diminished activity and chondrogenic differentiation capacity impede their therapeutic efficacy. Previous investigations have successfully shown that pretreatment with nanosecond pulsed electric fields (nsPEFs) significantly enhances the chondrogenic differentiation of MSCs. Therefore, this study aims to explore nsPEFs as a strategy to improve OA therapy by enhancing MSCs' activity and chondrogenic differentiation and also investigate its potential mechanism. Methods: In this study, a million MSCs were carefully suspended within a 0.4-cm gap cuvette and subjected to five pulses of nsPEFs (100 ns at 10 kV/cm, 1 Hz), with a 1-s interval between each pulse. A control group of MSCs was maintained without nsPEFs treatment for comparative analysis. nsPEFs were applied to regulate the MSCs performance and hinder OA progresses. In order to further explore the corresponding mechanism, we examined the changes of MSCs transcriptome after nsPEF pretreatment. Finally, we studied the properties of extracellular vesicles (EVs) secreted by MSCs affected by nsPEF and the therapeutic effect on OA. Results: We found that nsPEFs pretreatment promoted MSCs migration and viability, particularly enhancing their viability temporarily in vivo, which is also confirmed by mRNA sequencing analysis. It also significantly inhibited the development of OA-like chondrocytes in vitro and prevented OA progression in rat models. Additionally, we discovered that nsPEFs pretreatment reprogrammed MSC performance by enhancing EVs production (5.77 ± 0.92 folds), and consequently optimizing their therapeutic potential. Conclusions: In conclusion, nsPEFs pretreatment provides a simple and effective strategy for improving the MSCs performance and the therapeutic effects of MSCs for OA. EVs-nsPEFs may serve as a potent therapeutic material for OA and hold promise for future clinical applications. The translational potential of this article: This study indicates that MSCs pretreated by nsPEFs greatly inhibited the development of OA. nsPEFs pretreatment will be a promising and effective method to optimize the therapeutic effect of MSCs in the future.
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Depression has emerged as the predominant psychiatric affliction affecting individuals. Prior research has substantiated the antidepressant properties exhibited by numerous anesthetics. Sevoflurane, a widely utilized inhalant anesthetic in clinical practice, remains relatively uncharted in terms of its specific antidepressant effects. In this study, we used open field test, forced swimming test and novelty-suppressed feeding test to investigate the anxiety and depression-like behaviors in C57BL/6 mice following the inhalation of sevoflurane. We then used western blotting to scrutinized the expression levels of proteins associated with the brain-derived neurotrophic factor (BDNF)-tryosine receptor kinase B (TrkB) pathway in the hippocampus and prefrontal cortex. To further investigate whether sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway, we downregulated TrkB expression by administering siRNA into the lateral ventricle. We found that the inhalation of 2.5 % sevoflurane exerted a significant antidepressant-like effect, accompanied by an elevation in p-TrkB expression levels in the hippocampus and prefrontal cortex. Intriguingly, this antidepressant-like effect was abrogated following the downregulation of TrkB expression through the microinjection of siRNA into the lateral ventricle. In conclusion, this study provides evidence supporting the notion that sevoflurane exerts its antidepressant-like effect via the BDNF-TrkB signaling pathway.
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Fator Neurotrófico Derivado do Encéfalo , Depressão , Camundongos , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Sevoflurano/farmacologia , Receptor trkB/metabolismo , Camundongos Endogâmicos C57BL , Antidepressivos/farmacologia , Antidepressivos/metabolismo , Hipocampo/metabolismo , RNA Interferente Pequeno/metabolismo , Estresse Psicológico/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: Osteoarthritis is a common degenerative joint disease that is highly prevalent in the elderly population. Along with the occurrence of sports injuries, osteoarthritis is gradually showing a younger trend. Osteoarthritis has many causative factors, and its pathogenesis is currently unknown. Cellular senescence is a stable form of cell cycle arrest exhibited by cells in response to external stimuli and plays a role in a variety of diseases. And it is only in the last decade or so that cellular senescence has gradually become cross-linked with osteoarthritis. However, there is no comprehensive bibliometric analysis in this field. The aim of this study is to present the current status and research hotspots of cellular senescence in the field of osteoarthritis, and to predict the future trends of cellular senescence in osteoarthritis research from a bibliometric perspective. METHODS: This study included 298 records of cellular senescence associated with osteoarthritis from 2009 to 2023, with data from the Web of Science Core Collection database. CiteSpace, Scimago Graphica software, VOSviewer, and the R package "bibliometrix" software were used to analyze regions, institutions, journals, authors, and keywords to predict recent trends in cellular senescence related to osteoarthritis research. RESULTS: The number of publications related to cellular senescence associated with osteoarthritis is increasing year by year. China and the United States contribute more than 70% of the publications and are the mainstay of research in this field. Central South University is the most active institution with the largest number of publications. International Journal of Molecular Sciences is the most popular journal in the field with the largest number of publications, while Osteoarthritis and Cartilage is the most cited journal. Loeser, Richard F. is not only the most prolific author, but also the most frequently cited author, contributing greatly to the field. CONCLUSION: In the last decade or so, this is the first bibliometric study that systematically describes the current status and development trend of research on cellular senescence associated with osteoarthritis. The study comprehensively and systematically summarizes and concludes the research hotspots and development trends, providing valuable references for researchers in this field.
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Bibliometria , Senescência Celular , Osteoartrite , Osteoartrite/patologia , Senescência Celular/fisiologia , HumanosRESUMO
General anaesthetics have been widely applied to induce reversible loss and recovery of consciousness in clinical practice and have been shown to have reliably safe profiles. Since brief exposure to general anaesthetics can result in long-lasting and global changes in neuronal structures and function, these drugs also exhibit strong therapeutic potential for mood disorders. Preliminary and clinical studies have suggested that the inhalational anaesthetic drug sevoflurane might relieve symptoms of depression. However, the antidepressant effects of sevoflurane and the underlying mechanisms remain elusive. In the present study, we confirmed that the antidepressant and anxiolytic effects of inhaling 2.5% sevoflurane for 30 min were comparable to those of ketamine and could be sustained for 48 h. Activation of GABAergic (γ-aminobutyric acidergic) neurons in the nucleus accumbens core by chemogenetics was shown to mimic the antidepressant effects of inhaled sevoflurane, whereas inhibition of these neurons significantly prevented these effects. Considered together, these results suggested that sevoflurane might exert rapid and long-lasting antidepressant effects via modulation of neuronal activities in the nucleus accumbens core nucleus.
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Anestésicos Inalatórios , Núcleo Accumbens , Sevoflurano/farmacologia , Antidepressivos/farmacologia , Neurônios GABAérgicos , Anestésicos Inalatórios/farmacologiaRESUMO
Calycosin is a natural product extracted from some plant families and exhibits various biological properties. But the effect of calycosin on cerebral ischemia-reperfusion injury has not been fully elucidated. In this study, the neuroprotective effect of calycosin treatment on the differentiated SH-SY5Y cells exposed to OGD was evaluated using MTT and flow cytometry. Rats that were pretreatment with calycosin were subjected to MCAO, neurological behavior scores and brain infarct volume were evaluated. The protein expression of pERK/ERK were assessed using Western blot. siRNA-pERK and U0126 were administered to investigate the impact of the ERK pathway on calycosin preconditioning. The results demonstrated the neuronal viability in the calycosin-treated SH-SY5Y cells increased significantly, and the rate of apoptosis decreased compared with the Oxygen-glucose deprivation only SH-SY5Y cells. Calycosin pretreatment reduced infarct volume and improved neurological outcome in rats subjected to MCAO. Administration of calycosin increased the ratio of pERK/ERK expression, which was down-regulated in ischemia-reperfusion group. Down-regulation of pERK/ERK significantly attenuated the neuroprotective effect induced by calycosin pretreatment in vitro and in vivo. We concluded calycosin treatment could induce a neuroprotective effect against ischemia, which was related to the regulation of the ERK1/2 pathway.
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Isquemia Encefálica , Neuroblastoma , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Ratos , Humanos , Fármacos Neuroprotetores/farmacologia , Sistema de Sinalização das MAP Quinases , Isquemia Encefálica/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , ApoptoseRESUMO
The mechanism of general anesthesia remains elusive. The ventrolateral periaqueductal gray (vlPAG) in the midbrain regulates sleep and awake states. However, the role of vlPAG and its circuits in anesthesia is unclear. We utilized opto/chemogenetics, righting reflex, and electroencephalographic recording to assess consciousness changes. We employed fiber photometry to measure the activity of neurons and neurotransmitters. As a result, photometry recording showed that the activity of GABA neurons in vlPAG decreased during sevoflurane anesthesia and was reactivated after anesthesia. Activating GABAergic neurons in vlPAG promoted arousal during anesthesia, while inhibiting them delayed this process. Furthermore, medial prefrontal cortex (mPFC) to vlPAG pyramidal neurons projections and vlPAG to ventral tegmental area (VTA) GABAergic projections played a prominent role in the anesthesia-awake transition. GABA neurotransmitter activity of VTA synchronized with mPFC-vlPAG pyramidal neuron projections. Therefore, the cortico-midbrain circuits centered on vlPAG GABAergic neurons exert an arousal-promoting effect during sevoflurane anesthesia.
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BACKGROUND: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic. METHODS: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery. RESULTS: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic. LIMITATION: The absence of data from the early days of the COVID-19 outbreak. CONCLUSIONS: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period.
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BACKGROUND: Owing to limited self-healing capacity, failure of rotator cuff tendon healing is a common complication after surgery. Biological scaffolds have garnered attention owing to their potential to enhance healing outcomes. PURPOSE: To verify the effect of the decellularized umbilical cord Wharton jelly (DUCWJ) scaffold as a bridging scaffold in a rabbit model of acute rotator cuff tendon defect. STUDY DESIGN: Controlled laboratory study. METHODS: We fabricated a DUCWJ scaffold using a physicochemical decellularized method, evaluating changes in the umbilical cord Wharton jelly before and after decellularization. Scanning electron microscopy and biomechanical testing were performed to determine the microstructure and mechanical properties. We assessed cytocompatibility and cell regulatory behavior of the scaffold toward tendon stem/progenitor cells (TSPCs). A supraspinatus tendon defect was created in 54 New Zealand White rabbits, allocated to the DUCWJ scaffold repair group and the negative control group (without scaffold). Histology, reverse transcription polymerase chain reaction, and biomechanical tensile strength were assessed at 4, 8, and 12 weeks postoperatively. RESULTS: Decellularization completely removed cells from the umbilical cord Wharton jelly, retained a considerable amount of glycosaminoglycan and collagen, and preserved the microstructure and tensile strength. The DUCWJ scaffold facilitated migration and proliferation of TSPCs in vitro. Tendon-related gene expression revealed that the DUCWJ scaffold could maintain the tenocyte phenotype of TSPCs. In the in vivo study, the DUCWJ scaffold improved tendon healing and enhanced the biomechanical strength of repaired tendons. Histological evaluation scores of the DUCWJ group were significantly higher than those of the negative control at 4, 8, and 12 weeks after surgery (P < .05). In repaired tendon tissues, reverse transcription polymerase chain reaction findings revealed that the DUCWJ scaffold stimulated tendon development and maturation. Furthermore, an overall increase in ultimate load and tensile modulus was noted over time; the DUCWJ group presented better results than the negative control group (P < .05). CONCLUSION: The DUCWJ scaffold has an excellent 3-dimensional porous structure, good biocompatibility, and fundamental biomechanical characteristics, and it promotes migration, attachment, and proliferation of TSPCs. The in vivo animal study demonstrated that the DUCWJ scaffold has potential for tendon regeneration in an acute rotator cuff tendon defect model. CLINICAL RELEVANCE: DUCWJ scaffolds have potential as a regenerative material to augment rotator cuff healing in the clinical setting.
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Lesões do Manguito Rotador , Geleia de Wharton , Animais , Fenômenos Biomecânicos , Humanos , Coelhos , Manguito Rotador/patologia , Lesões do Manguito Rotador/metabolismo , Lesões do Manguito Rotador/cirurgia , Tendões/patologia , Cordão Umbilical , CicatrizaçãoRESUMO
Developing light structure materials that work stably at elevated temperatures is a long-standing challenge for many application fields, particularly in the development of aerospace equipment. Zn/Cd alloying elements were prospected to improve the stability of the lightest Mg-Li based alloys; however, little is known about the intermediate-temperature mechanical properties of such alloys. The present work investigated the tensile behaviors of a cold-rolled Mg-Li-Al-Cd-Zn alloy in a temperature range of 30-150 °C. The results indicate that the alloy can host a tensile strength σUTS of 108~121 MPa, a yield strength σYP of 97~109 MPa and elongation εB of 14-15 % at 150 °C, dependent on the tensile direction. The mechanical properties intensively are modulated by temperature through the competition between work hardening and softening. Work hardening due to dislocation blocking by the precipitated MgLi2X phase dominated the deformation at low temperatures, while softening that resulted from dynamic recrystallization was the main effect at high temperatures. Correspondingly, a quasi-cleavage mechanism dominated the fracture at temperatures near room temperature, and microvoid coalescence worked at high temperatures above 100 °C. Our results offer a new experimental understanding of the elevated-temperature mechanical behaviors of Mg-Li alloys and will advance the development of new light magnesium alloys with high stability.
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Dopaminergic neurons in the ventral tegmental area (VTA) play an important role in cognition, emergence from anesthesia, reward, and aversion, and their projection to the cortex is a crucial part of the "bottom-up" ascending activating system. The prelimbic cortex (PrL) is one of the important projection regions of the VTA. However, the roles of dopaminergic neurons in the VTA and the VTADA-PrL pathway under sevoflurane anesthesia in rats remain unclear. In this study, we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist (Chloro-APB) into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats, while injection of a dopamine D1 receptor antagonist (SCH23390) deepened anesthesia. The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA-PrL pathway prolonged the induction time and shortened the emergence time of anesthesia. These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA-PrL pathway facilitates emergence from sevoflurane anesthesia.
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Anestesia , Neurônios Dopaminérgicos , Animais , Neurônios Dopaminérgicos/metabolismo , Ratos , Receptores de Dopamina D1/metabolismo , Sevoflurano/farmacologia , Área Tegmentar Ventral/metabolismoRESUMO
CNS inflammation is known to be an important pathogenetic mechanism of perioperative neurocognitive disorder (PND), and iron overload was reported to participate in this process accompanied by oxidative stress. Ferroptosis is an iron-dependent form of cell death, and occurs in multiple neurodegenerative diseases with cognitive disorder. However, the effect of ferroptosis in inflammation-related PND is unknown. In this study, we found that the ferroptosis inhibitor liproxstatin-1 ameliorated memory deficits in the mouse model of lipopolysaccharide (LPS)-induced cognitive impairment. Moreover, liproxstatin-1 decreased the activation of microglia and the release of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF)-α, attenuated oxidative stress and lipid peroxidation, and further weakened mitochondrial injury and neuronal damage after LPS exposure. Additionally, the protective effect of liproxstatin-1 was related to the alleviation of iron deposition and the regulation of the ferroptosis-related protein family TF, xCT, Fth, Gpx4, and FtMt. These findings enhance our understanding of inflammation-involved cognitive dysfunction and shed light on future preclinical studies.
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Disfunção Cognitiva , Ferroptose , Camundongos , Animais , Lipopolissacarídeos/toxicidade , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Inflamação/metabolismo , Ferro/metabolismoRESUMO
Metabolic alteration of articular cartilage is associated with the pathogenesis of Osteoarthritis (OA). This study aims to identify the metabolism-related genes, corresponding transcription factors (TFs), and relevant pathways. Overall, RNA sequencing profiles of articular cartilage were collected from the GEO database. Metabolism-related genes and OA-related hallmarks were collected from the MSigDB v7.1. Differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Gene Set Variation Analysis (GSVA) were conducted to identify pathways or hallmarks that were related to the pathogenesis of OA. The Pearson correlation analysis was used to establish the regulatory network among transcription factors, metabolism-related genes, and hallmarks. To further confirm the regulation of the identified transcription factors, Chromatin Immunoprecipitation-sequencing (ChIP-seq) was conducted, and single-cell sequencing was used to locate the cell clusters. Connectivity Map (CM) analysis were also conducted to identify the potential specific bioactive small molecules targeting the metabolic alteration of osteoarthritis. scTPA database was used to detect activated signaling pathways. Collectively, a total of 74 and 38 differentially expressed metabolism-related genes and TFs were retrieved. Skeletal system development, extracellular matrix, and cell adhesion molecule binding were important pathways in GO analysis. Human papillomavirus infection, PI3K-Akt signaling pathway, and Human T-cell leukemia virus 1 infection were the top 3 pathways in KEGG. 7 and 12 hallmarks were down- and up-regulated in GSVA, respectively. Ten bioactive small molecules may be potential treatments of OA by regulating the metabolism of articular cartilage. ChIP-seq analysis showed high relativity between transcription factors and their target genes. Furthermore, single-cell sequencing confirms the high expression of identified transcription factors in chondrocytes. To conclude, we established a comprehensive network integrated with transcription factors, metabolism-related genes, and hallmarks.