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Oxidative stress is closely related to various diseases. Ozone can produce redox reactions through its unique response. As a source of the oxidative stress response, the strong oxidizing nature of ozone can cause severe damage to the body. On the other hand, low ozone concentrations can activate various mechanisms to combat oxidative stress and achieve therapeutic effects. Some animal experiments and clinical studies have revealed the potential medical value of ozone, indicating that ozone is not just a toxic gas. By reviewing the mechanism of ozone and its therapeutic value in treating central nervous system diseases (especially ischemic stroke and Alzheimer's disease) and the toxic effects of ozone, we find that ozone inhalation and a lack of antioxidants or excessive exposure lead to harmful impacts. However, with adequate antioxidants, ozone can transmit oxidative stress signals, reduce inflammation, reduce amyloid ß peptide levels, and improve tissue oxygenation. Similar mechanisms to those of possible new drugs for treating ischemic stroke and Alzheimer's disease indicate the potential of ozone. Nevertheless, limited research has restricted the application of ozone. More studies are needed to reveal the exact dose-effect relationship and healing effect of ozone.
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Doenças do Sistema Nervoso Central , Estresse Oxidativo , Ozônio , Ozônio/farmacologia , Humanos , Animais , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologiaRESUMO
Postoperative adhesion is a common clinical disease caused by surgical trauma, accompanying serious subsequent complications. Current non-surgical drug therapy and biomaterial barrier administration have limited therapeutic effects due to their inherent deficiencies. Therefore, developing a simple, effective, and feasible method to effectively prevent postoperative adhesions after surgical procedures remains a challenge. An injectable chondroitin sulfate complex hydrogel was prepared based on aldehyde-modified chondroitin sulfate (ChS-CHO) and hydrazine-modified chondroitin sulfate (ChS-ADH). The hydrogel showed enhanced strength and good self-healing ability. By using the Schiff base reaction principle that aldehyde group reacts with hydrazide to form hydrazone bond, C-A hydrogel physical barrier is formed at the wound site to reduce the occurrence of postoperative adhesion. There is no use of chemical crosslinkers in the whole reaction system to prepare C-A hydrogel, which has excellent biocompatibility and is safe and non-toxic. The results showed that C-A hydrogel showed excellent mechanical properties, good self-healing, and biocompatibility. The cecal-abdominal wall adhesion model and hepatic adhesion model of rats were constructed respectively to evaluate its preventive effect on postoperative adhesion. The results showed that C-A hydrogel had a more significant preventive effect on postoperative adhesion, and appears to be a promising candidate for postoperative adhesion.
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In 2009, the World Health Organization included snakebite on the list of neglected tropical diseases, acknowledging it as a common occupational hazard for farmers, plantation workers, and others, causing tens of thousands of deaths and chronic physical disabilities every year. This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims. These recommendations are based on clinical experience and clinical research evidence. This guideline focuses on the following topics: snake venom, clinical manifestations, auxiliary examination, diagnosis, treatments, and prevention.
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Purpose: This case report aimed to summarize the risk factors, clinical characteristics, imaging changes, and maternal and fetal prognosis associated with Moyamoya disease in pregnant women and to explore effective management strategies and a comprehensive delivery plan. Case Presentation: The clinical data of four pregnant women who were diagnosed with Moyamoya disease and admitted to our hospital between January 2010 and January 2019 were retrospectively analyzed. Their diagnosis, treatment, delivery, and postpartum management during the pregnancy were analyzed. Among the four pregnant women, three were primipara and one was multipara. The age ranged from 27 to 41 years old. The gestational week of termination of pregnancy ranged between 8 and 39 weeks. During pregnancy, one case died in utero; one case was complicated with postpartum hemorrhage; one case was complicated with chronic hypertension, multiple cerebral artery stenosis and occlusion, bilateral middle cerebral artery occlusion, bilateral internal carotid artery occlusion, and Hashimoto's thyroiditis. Under epidural anesthesia, two cases underwent a lower segment cesarean section; one case underwent artificial abortion; and one case underwent induced labor during late pregnancy. Two newborns survived. Conclusion: Moyamoya disease is a rare and serious complication of pregnancy. Pregnancy and childbirth may exacerbate the progression of this disease or induce cerebrovascular accidents, with a high mortality and disability rate, which seriously threatens the safety of mother and infant lives; however, with the close collaboration of a multidisciplinary team, it is possible to maximize a good pregnancy outcome.
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Population pharmacokinetic (PK) models are widely used to inform drug development by pharmaceutical companies and facilitate drug evaluation by regulatory agencies. Developing a population PK model is a multi-step, challenging, and time-consuming process involving iterative manual model fitting and evaluation. A tool for fully automatic model development (AMD) of common population PK models is presented here. The AMD tool is implemented in Pharmpy, a versatile open-source library for pharmacometrics. It consists of different modules responsible for developing the different components of population PK models, including the structural model, the inter-individual variability (IIV) model, the inter-occasional variability (IOV) model, the residual unexplained variability (RUV) model, the covariate model, and the allometry model. The AMD tool was evaluated using 10 real PK datasets involving the structural, IIV, and RUV modules in three sequences. The different sequences yielded generally consistent structural models; however, there were variations in the results of the IIV and RUV models. The final models of the AMD tool showed lower Bayesian Information Criterion (BIC) values and similar visual predictive check plots compared with the available published models, indicating reasonable quality, in addition to reasonable run time. A similar conclusion was also drawn in a simulation study. The developed AMD tool serves as a promising tool for fast and fully automatic population PK model building with the potential to facilitate the use of modeling and simulation in drug development.
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Teorema de Bayes , Simulação por Computador , Modelos Biológicos , Farmacocinética , Humanos , Desenvolvimento de Medicamentos/métodos , SoftwareRESUMO
Programmed death-ligand 1 (PD-L1) has emerged as a promising therapeutic target for various cancers due to its crucial role in promoting tumor immune evasion. Here, we report a novel class of chroman-like small-molecule PD-L1 inhibitors exhibiting significant activity in inhibiting the PD-1/PD-L1 interaction. Employing a "ring-close" strategy for conformational restriction, we have achieved compound C27, which demonstrates superior PD-1/PD-L1 inhibitory activity compared to the positive control. Molecular dynamics simulation and binding free energy calculation predict that (R)-C27 with inhibitory activity surpassed (S)-C27. The experimental results from bioassay and X-ray structural analysis corroborate these findings. All these results collectively indicate that (R)-C27 is a promising lead compound deserving further exploration.
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Antígeno B7-H1 , Cromanos , Desenho de Fármacos , Receptor de Morte Celular Programada 1 , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Humanos , Cromanos/química , Cromanos/farmacologia , Simulação de Dinâmica MolecularRESUMO
The identification of the non-noble metal constituted TaO cluster as a potential analogue to the noble metal Au is significant for the development of tailored materials. It leverages the superatom concept to engineer properties with precision. However, the impact of incrementally integrating TaO units on the electronic configurations and properties within larger TaO-based clusters remains to be elucidated. By employing the density functional theory calculations, the global minima and low-lying isomers of the TanOn (n = 2-5) clusters were determined, and their structural evolution was disclosed. In the cluster series, Ta5O5 was found to possess the highest electron affinity (EA) with a value of 2.14 eV, based on which a dual external field (DEF) strategy was applied to regulate the electronic property of the cluster. Initially, the electron-withdrawing CO ligand was affixed to Ta5O5, followed by the application of an oriented external electric field (OEEF). The CO ligation was found to be able to enhance the Ta5O5 cluster's electron capture capability by adjusting its electron energy levels, with the EA of Ta5O5(CO)4 peaking at 2.58 eV. Subsequently, the introduction of OEEF further elevated the EA of the CO-ligated cluster. Notably, OEEF, when applied along the +x axis, was observed to sharply increase the EA to 3.26 eV, meeting the criteria for superhalogens. The enhancement of EA in response to OEEF intensity can be quantified as a functional relationship. This finding highlights the advantage of OEEF over conventional methods, demonstrating its capacity for precise and continuous modulation of cluster EAs. Consequently, this research has adeptly transformed tantalum oxide clusters into superhalogen structures, underscoring the effectiveness of the DEF strategy in augmenting cluster EAs and its promise as a viable tool for the creation of superhalogens.
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Objective: In this study, we investigated the value of molecular typing combined with integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) semi-quantitative indices in endometrial cancer risk stratification. Methods: A retrospective study was conducted on 86 patients who were pathologically diagnosed with endometrial cancer and underwent surgical treatment after curettage at the Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University between January 2017 and March 2023. Prior to surgery, each patient underwent integrated PET/MRI examination. The postoperative samples were subjected to pathological diagnosis, immunohistochemistry, and POLE gene sequencing. The differences in clinicopathological features between the four molecular subtypes and the differences in integrated PET/MRI semi-quantitative indexes (SUV max, ADC min) between the four molecular subtypes were analyzed. The cutoff value of molecular typing combined with integrated PET/MRI semi-quantitative indices for endometrial cancer risk stratification was determined. Results: There were statistically significant differences in pathological types and tumor grades among the four molecular subtypes of endometrial cancer. The values of the four integrated PET/MRI semi-quantitative indices (SUV max and ADC min) of the molecular subtypes were statistically different. The SUV max was greater in the p53abn mutation group than in the POLE mutation group (P < 0.05). The ADC minimum of the POLE mutation group and the MMR-d group was lower than the NSMP group (P < 0.05). Molecular typing combined with the integrated PET/MRI semi-quantitative SUV max index can predict the low/medium risk group of endometrial cancer and the medium-high/high risk group, and the cut-off value of SUV max for predicting the risk of early endometrial cancer was 14.72 (sensitivity 66.7%, specificity 68.7%). Conclusion: Molecular typing combined with integrated PET/MRI semi-quantitative indicators is useful to achieve risk stratification in patients diagnosed with endometrial cancer and guide individualized treatment.
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Hierarchical biobased micro/nanomaterials offer great potential as the next-generation building blocks for robust films or macroscopic fibers with high strength, while their capability in suppressing crack propagation when subject to damage is hindered by their limited length. Herein, we employed an approach to directly convert bulk wood into fibers with a high aspect ratio and nanosized branching structures. Particularly, the length of microfibers surpassed 1 mm with that of the nanosized branches reaching up to 300 µm. The presence of both interwoven micro- and nanofibers endowed the product with substantially improved tensile strength (393.99 MPa) and toughness (19.07 MJ m-3). The unique mechanical properties arose from mutual filling and the hierarchical deformation facilitated by branched nanofibers, which collectively contributed to effective energy dissipation. Hence, the nanotransformation strategy opens the door toward a facial, scalable method for building high-strength film or macroscopic fibers available in various advanced applications.
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Numerous neurological disorders share a fatal pathologic process known as glutamate excitotoxicity. Among which, ischemic stroke is the major cause of mortality and disability worldwide. For a long time, the main idea of developing anti-excitotoxic neuroprotective agents was to block glutamate receptors. Despite this, there has been little successful clinical translation to date. After decades of "neuron-centered" views, a growing number of studies have recently revealed the importance of non-neuronal cells. Glial cells, cerebral microvascular endothelial cells, blood cells, and so forth are extensively engaged in glutamate synthesis, release, reuptake, and metabolism. They also express functional glutamate receptors and can listen and respond for fast synaptic transmission. This broadens the thoughts of developing excitotoxicity antagonists. In this review, the critical contribution of non-neuronal cells in glutamate excitotoxicity during ischemic stroke will be emphasized in detail, and the latest research progress as well as corresponding therapeutic strategies will be updated at length, aiming to reconceptualize glutamate excitotoxicity in a non-neuronal perspective.
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Ácido Glutâmico , AVC Isquêmico , Humanos , Animais , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Ácido Glutâmico/metabolismo , Neuroglia/metabolismo , Neuroglia/patologia , Neurônios/metabolismo , Neurônios/patologiaRESUMO
Flat membranes ubiquitously transform into mysterious complex shapes in nature and artificial worlds. Behind the complexity, clear determinative deformation modes have been continuously found to serve as basic application rules but remain unfulfilled. Here, we decipher two elemental deformation modes of thin membranes, spontaneous scrolling and folding as passing through shrinking channels. We validate that these two modes rule the deformation of membranes of a wide thickness range from micrometer to atomic scale. Their occurrence and the determinative fold number quantitatively correlate with the Föppl-von Kármán number and shrinkage ratio. The unveiled determinative deformation modes can guide fabricating foldable designer microrobots and delicate structures of two-dimensional sheets and provide another mechanical principle beyond genetic determinism in biological morphogens.
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Objective: To review and summarize the characteristics and therapy of paraganglioma of the urinary bladder (PUB). Method: Patients who underwent the operation in Peking Union Medical College Hospital between January 2012 and December 2021 were reviewed for this retrospective study. Results: A total of 29 patients, comprising 9 (31%) men and 20 (69%) women, were included. The main manifestations were hypertension, palpitation, and micturition syncope. Eight patients had an increased 24-h urinary catecholamine, and seven of them had increased norepinephrine. Normetanephrine in seven patients was increased. Six of 18 metaiodobenzylguanidine and 8 of 22 octreotide scans were positive. In total, 15 cases underwent laparoscopic partial cystectomy and 14 underwent transurethral resection of bladder tumor. In all patients, the immunohistochemical index of Melan-A, AE1/AE3, and α-inhibin were negative, and chromogranin A, S-100, and succinate dehydrogenase were positive. The Ki-67 of 28/29 cases was under 5%, and 1 case with a Ki-67 of 20% was diagnosed with malignant PUB. A total of 27 patients had a regular follow-up, 2 patients were lost during the follow-up, 3 patients had a recurrence, and 1 of these patients died within 1 year of surgery. The symptoms all disappeared or were relieved after the surgery. Conclusion: The transurethral surgery approach fits PUB tumors with a size <3â cm or that protrudes into the bladder and can significantly reduce the postoperative hospital stay. Early detection and treatment are effective, and regular review is necessary after the surgery.
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Programmed death-ligand 1 (PD-L1) has surfaced as a promising therapeutic target for various cancers due to its pivotal role in facilitating tumor immune evasion. Herein, we report a series of novel small-molecule PD-L1 inhibitors exhibiting remarkable inhibitory activity against the PD-1/PD-L1 interaction (X18: IC50 = 1.3 nM) and reinstating the suppressive effect of PD-L1 on T cells (X18: EC50 = 152.8 nM). Crystallographic studies revealed the binding mode of X18 and PD-L1. Through a rational prodrug design approach, we have successfully optimized the oral pharmacokinetic properties of X22, effectively addressing the poor oral pharmacokinetic profile of PD-L1 small-molecule inhibitors. Notably, X22 demonstrated significant antitumor efficacy in murine models of MC38 and CT26 colon cancer through the upregulation of tumor infiltration and cytotoxicity of CD8+ T cells partially. These findings offer promising prospects for the advancement of PD-L1 inhibitors as innovative agents in cancer immunotherapy.
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Neoplasias do Colo , Inibidores de Checkpoint Imunológico , Animais , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Linfócitos T CD8-Positivos , Antígeno B7-H1 , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismoRESUMO
Clonal integration of defense or stress signal induced systemic resistance in leaf of interconnected ramets. However, similar effects of stress signal in root are poorly understood within clonal network. Clonal fragments of Centella asiaticas with first-young, second-mature, third-old and fourth-oldest ramets were used to investigate transportation or sharing of stress signal among interconnected ramets suffering from low water availability. Compared with control, oxidative stress in root of the first-young, second-mature and third-old ramets was significantly alleviated by exogenous ABA application to the fourth-oldest ramets as well as enhancement of antioxidant enzyme (SOD, POD, CAT and APX) activities and osmoregulation ability. Surface area and volume in root of the first-young ramets were significantly increased and total length in root of the third-old ramets was significantly decreased. POD activity in root of the fourth-oldest and third-old ramets was significantly enhanced by exogenous ABA application to the first-young ramets. Meanwhile, total length and surface area in root of the fourth-oldest and third-old ramets were significantly decreased. Ratio of belowground to aboveground biomass in the whole clonal fragments was significantly increased by exogenous ABA application to the fourth-oldest or first-young ramets. It is suggested that transportation or sharing of stress signal may induce systemic resistance in root of interconnected ramets. Specially, transportation or sharing of stress signal against phloem flow was observed in the experiment. Possible explanation is that rapid recovery of foliar photosynthesis in first-young ramets subjected to exogenous ABA application can partially reverse phloem flow within clonal network. Thus, our experiment provides insight into ecological implication on clonal integration of stress signal.
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Antioxidantes , Centella , Ansiedade , Biomassa , OsmorregulaçãoRESUMO
The mechanical behaviors of 2D materials are fundamentally important for their potential applications in various fields. α-Molybdenum trioxide (α-MoO3) crystals with unique electronic, optical, and electrochemical properties, have attracted extensive attention for their use in optoelectronic and energy conversion devices. From a mechanical viewpoint, however, there is limited information available on the mechanical properties of α-MoO3. Here, we developed a capillary force-assisted peeling method to directly transfer α-MoO3 nanosheets onto arbitrary substrates. Comparatively, we could effectively avoid surface contamination arising from the polymer-assisted transfer method. Furthermore, with the help of an in situ push-to-pull (PTP) device during SEM, we systematically investigated the tensile properties of α-MoO3. The measured Young's modulus and fracture strengths along the c-axis (91.7 ± 13.7 GPa and 2.1 ± 0.9 GPa, respectively) are much higher than those along the a-axis (55.9 ± 8.6 GPa and 0.8 ± 0.3 GPa, respectively). The in-plane mechanical anisotropy ratio can reach â¼1.64. Both Young's modulus and the fracture strength of MoO3 show apparent size dependence. Additionally, the multilayer α-MoO3 nanosheets exhibited brittle fracture with interplanar sliding due to poor van der Waals interaction. Our study provides some key points regarding the mechanical properties and fracture behavior of layered α-MoO3 nanosheets.
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Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic interventions. The Wnt signaling pathway exhibits extensive crosstalk with various other pathways, forming a network system of signaling pathways involved in I/R injury. This review article elucidates the underlying mechanisms involved in Wnt signaling, as well as the complex interplay between Wnt and other pathways, including Notch, phosphatidylinositol 3-kinase/protein kinase B, transforming growth factor-ß, nuclear factor kappa, bone morphogenetic protein, N-methyl-D-aspartic acid receptor-Ca2+-Activin A, Hippo-Yes-associated protein, toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-ß, and hepatocyte growth factor/mesenchymal-epithelial transition factor. In particular, we delve into their respective contributions to key pathological processes, including apoptosis, the inflammatory response, oxidative stress, extracellular matrix remodeling, angiogenesis, cell hypertrophy, fibrosis, ferroptosis, neurogenesis, and blood-brain barrier damage during I/R injury. Our comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery, while activation of the non-canonical Wnt pathways exacerbates injury. Moreover, we explore novel therapeutic approaches based on these mechanistic findings, incorporating evidence from animal experiments, current standards, and clinical trials. The objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction, to facilitate the development of innovative therapeutic agents for I/R injury.
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Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/genética , Reperfusão , Via de Sinalização Wnt/genética , Apoptose/genética , IsquemiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SLBZS) is a formula of traditional Chinese medicine (TCM) that enhances the functions of the qi, spleen, and lung. According to the theory of TCM, chronic obstructive pulmonary disease (COPD) is often caused by lung qi deficiency, and SLBZS is often used in the treatment of COPD and has achieved remarkable results. However, the active components of SLBZS absorbed in serum and the underlying mechanism of SLBZS in treating COPD remain unclear and require further studies. AIM OF THE STUDY: The objective of this study is to investigate the active components of SLBZS in rat serum, as well as the crucial targets and signaling pathways involved in the therapeutic effects of SLBZS for COPD. MATERIALS AND METHODS: First, the absorption components and metabolites of SLBZS in rat serum were identified using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Second, potential targets of SLBZS for the treatment of COPD were acquired from publicly accessible online sources. Cytoscape (v3.7.0) software was used to construct a component-target-pathway network and a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of potential targets was performed using the Metascape database. The binding status of the active components in SLBZS to the potential targets was assessed with molecular docking technology. Finally, a cell model of COPD was successfully developed for experimental validation In vitro. RESULTS: A total of 108 active components were identified, including 30 prototype components and 78 metabolites. A total of 292 potential targets for the treatment of COPD were identified, including TNF, IL-6, TLR9, RELA, and others. The KEGG pathway included inflammatory mediator regulation of TRP channels, necroptosis, and the NF-κB signaling pathway, among others. The In vitro experiments showed that SLBZS-containing serum had the ability to decrease the levels of inflammatory factors and cell death. Additionally, it was observed that SLBZS-containing serum could control the expression levels of TLR9, MyD88, TRAF6, NF-κB, and IκBα at the mRNA and protein levels. These findings suggested that SLBZS-containing serum was likely to be involved in the regulation of the TLR9/NF-κB pathway. CONCLUSIONS: The mechanism of action of SLBZS on COPD was preliminarily elucidated using UPLC-Q-TOF-MS/MS, network pharmacology, and In vitro experiments. The primary active components and potential targets of SLBZS were identified, providing a scientific foundation for further research.
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Medicamentos de Ervas Chinesas , Doença Pulmonar Obstrutiva Crônica , Animais , Ratos , Espectrometria de Massas em Tandem , Farmacologia em Rede , NF-kappa B , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Receptor Toll-Like 9 , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológicoRESUMO
Cellulose-based composites have attracted significant attention in the fabrication and advancement of wearable devices due to their sustainable, degradable, and cost-effective properties. However, achieving a cellulosic sensor with reliable sensory feedback remains challenging owing to the deficiency in reversible microstructures during response processes. In this study, we developed a piezoresistive sensor consisting of nearly pure cellulose handsheets using origami-inspired corrugated structures to achieve durable and sensitive piezoresistive responses. Multi-walled carbon nanotubes (MWCNTs) were used as conducting agents. With the addition of 7 wt% MWCNTs, 36.27 % of the cellulose fiber surface was covered and the conductivity of cellulose handsheets was increased to 8.7 S/m. The obtained conductive cellulose handsheets were transformed into corrugated structures and integrated orthogonally to construct the piezoresistive sensors with reversible electrical paths for electrons. The restorable corrugated structure endowed the sensors with a wide workable pressure range (0-10 kPa), high sensitivity (6.09 kPa-1 in a range of 0-0.92 kPa), fast response time (<280 ms), and good durability (>1000 cycles). Furthermore, the practical applications of the proposed sensors as wearable devices were demonstrated through phonation, real-time sports monitoring, and step pressure tests.
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BACKGROUND: In China, traditional Chinese medicines (TCMs), as a complementary therapy combined with chemotherapy, is widely used in the treatment of gastric cancer (GC). In order to systematically evaluate and synthesize existing evidence to provide a scientific basis for the efficacy and safety of this complementary therapy, we present an overview of systematic reviews (SRs) and meta-analyses (MAs) on the topic of TCMs as a complementary therapy in combination with chemotherapy for the treatment of GC. METHODS: SRs/MAs on TCMs combined with chemotherapy for GC were comprehensively searched in 8 databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Thirteen published SRs/MAs were included in our study. In terms of methodology, all SRs/MAs were considered to be of very low quality. Only 3 SRs/MAs has been assessed as low risk of bias. None of the SRs/MAs has been fully reported on the checklist. A total of 97 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. CONCLUSIONS: TCMs may be an effective and safe complementary therapy in combination with chemotherapy for the treatment of GC. However, this conclusion must be treated with caution as the quality of the evidence provided by SRs/MAs is generally low.
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Terapia por Acupuntura , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Medicina Tradicional Chinesa , China , Bases de Dados FactuaisRESUMO
Parkinson's disease (PD) is a common neurodegenerative pathology whose major clinical symptoms are movement disorders. The main pathological characteristics of PD are the selective death of dopaminergic (DA) neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein (α-Syn) within these neurons. PD is associated with numerous risk factors, including environmental factors, genetic mutations and aging. In many cases, the complex interplay of numerous risk factors leads to the onset of PD. The mutated α-Syn gene, which expresses pathologicalα-Syn protein, can cause PD. Another important feature of PD is neuroinflammation, which is conducive to neuronal death. α-Syn is able to interact with certain cell types in the brain, including through phagocytosis and degradation of α-Syn by glial cells, activation of inflammatory pathways by α-Syn in glial cells, transmission of α-Syn between glial cells and neurons, and interactions between peripheral immune cells and α-Syn. In addition to the aforementioned risk factors, PD may also be associated with aging, as the prevalence of PD increases with advancing age. The aging process impairs the cellular clearance mechanism, which leads to chronic inflammation and the accumulation of intracellular α-Syn, which results in DA neuronal death. In the present review, the age-associated α-Syn pathogenicity and the interactions between α-Syn and certain types of cells within the brain are discussed to facilitate understanding of the mechanisms of PD pathogenesis, which may potentially provide insight for the future clinical treatment of PD.