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PURPOSE: This paper describes the implementation of an instantaneous low-dose-rate total body irradiation (TBI) technique using block-filtered 6 MV X-rays with a linear accelerator (LINAC) to reduce pulmonary toxicity. METHODS: In the absence of dedicated TBI-specific meter-set dose rates in LINAC and sufficient treatment room size, a 2-cm-thick transmission block was used together with a 200-cm source-to-surface distance (SSD) to reduce the instantaneous dose rates of 6 MV x-rays down to 10 cGy/min, thus alteration to the beam properties. A TBI-specific dose calculation model was built with data acquired at the treatment planning system (TPS)-permitted maximum 140-cm SSD and was validated in phantoms at a 180-cm SSD. As for planning strategies, we adopted large anterior-to-posterior/posterior-to-anterior (AP/PA) open fields with multi-leaf collimator shielding for lungs to achieve target coverage, lung protection, and efficient dose delivery. A custom-designed sliding couch (Patent No. ZL202123085880.1) was manufactured to support patients during treatment. Measures to control the quality and safety of TBI treatment include machine interlocks, pretreatment checklists, and in-vivo dose monitoring. RESULTS: The instantaneous dose rate of block-filtered 6MV X-ray was reduced to approximately 7.0 cGy/min at 12.5-7.5 cm depth with a 185-200 cm SSD. The dose calculated by TPS differs from the measurements by 0.15%-1.55% in the homogeneous phantom and 1.2%-4.85% in the CIRS thorax phantom. The open-field TBI technique achieved V90% (PTV) ≈ 96.8% and MLD = 6.6 Gy with 1-h planning and 50-min beam delivery in a single fraction. From February 2021 to July 2023, 30 patients received TBI treatments in our center, and in-vivo monitoring results differed from TPS calculations by -1.49%-2.10%. After 6-12 months of follow-ups, all the patients treated in our center showed no pulmonary toxicities of grade 2 or higher. CONCLUSION: A low instantaneous dose rate TBI technique can be implemented in the clinic.
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Reusable point-of-care biosensors offer a cost-effective solution for serial biomarker monitoring, addressing the critical demand for tumour treatments and recurrence diagnosis. However, their realization has been limited by the contradictory requirements of robust reusability and high sensing capability to multiple interactions among transducer surface, sensing probes and target analytes. Here we propose a drug-mediated organic electrochemical transistor as a robust, reusable epidermal growth factor receptor sensor with striking sensitivity and selectivity. By electrostatically adsorbing protonated gefitinib onto poly(3,4-ethylenedioxythiophene):polystyrene sulfonate and leveraging its strong binding to the epidermal growth factor receptor target, the device operates with a unique refresh-in-sensing mechanism. It not only yields an ultralow limit-of-detection concentration down to 5.74 fg ml-1 for epidermal growth factor receptor but, more importantly, also produces an unprecedented regeneration cycle exceeding 200. We further validate the potential of our devices for easy-to-use biomedical applications by creating an 8 × 12 diagnostic drug-mediated organic electrochemical transistor array with excellent uniformity to clinical blood samples.
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Aims: Nattokinase (NK), a potent serine endopeptidase, has exhibited a variety of pharmacological effects, including thrombolysis, anti-inflammation, and antioxidative stress. Building on previous research highlighting NK's promise in nerve regeneration, our study investigated whether NK exerted protective effects in transient middle cerebral artery occlusion (tMCAO)-induced cerebral ischemia-reperfusion injury and the underlying mechanisms. Results: The rats were administered NK (5000, 10000, 20000 FU/kg, i.g., 7 days before surgery, once daily). We showed that NK treatment dose dependently reduced the infarction volume and improved neurological symptoms, decreased the proinflammatory and coagulation cytokines levels, and attenuated reactive oxygen species (ROS) in the infarcted area of tMCAO rats. We also found that NK could exert neuroprotective effects in a variety of vitro models, including the microglia inflammation model and neuronal oxygen-glucose deprivation/reperfusion (OGD/R) model. Notably, NK effectively countered OGD/R-induced neuron death, modulating diverse pathways, including autophagy, apoptosis, PARP-dependent death, and endoplasmic reticulum stress. Furthermore, the neuroprotection of NK was blocked by phenylmethylsulfonyl fluoride (PMSF), a serine endopeptidase inhibitor. We revealed that heat-inactive NK was unable to protect against tMCAO injury and other vitro models, suggesting NK attenuated ischemic injury by its enzymatic activity. We conducted a proteomic analysis and found inflammation and coagulation were involved in the occurrence of tMCAO model and in the therapeutic effect of NK. Innovation and Conclusion: In conclusion, these data demonstrated that NK had multifaceted neuroprotection in ischemic brain injury, and the therapeutic effect of NK was related with serine endopeptidase activity.
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Engineering black carbon (e.g. biochar) has been widely found in natural environments due to natural processes and extensive applications in engineering systems, and could influence the geochemical processes of coexisting arsenic (AsV) and FeII, especially when they are exposed to oxic conditions. Here, we studied time-varying kinetics and efficiencies of AsV immobilization by solid-phase FeII (FeIIsolid) and FeIII (FeIIIsolid) in FeII-AsV-biochar systems under both anoxic and oxic conditions at pH 7.0, with focuses on the effects of biochar surface and biochar-derived dissolved organic carbon (DOC). Under anoxic conditions, FeII could rapidly immobilize AsV via co-adsorption onto biochar surfaces, which also serves as the dominant pathway of AsV immobilization at the initial stage of reaction (0-5 min) under oxic conditions at high biochar concentrations. Subsequently, with increasing biochar concentrations, FeIIIsolid precipitation from aqueous FeII (FeIIaq) oxidation (5-60 min) starts to play an important role in AsV immobilization but in decreased efficiencies of AsV immobilization per unit iron. In the following stage (60-300 min), FeIIsolid oxidation is suppressed and leads to AsV release into solutions at >1.0 g·L-1 biochar. The decreasing efficiency of AsV immobilization over time is attributed to the gradual release of DOC into solution from biochar particles, which significantly inhibit AsV immobilization when FeIIIsolid is generated from FeIIsolid oxidation in the vicinity of biochar surfaces. Specifically, 4.06 mg·L of biochar-derived DOC can completely inhibit the immobilization of AsV in the 100 µM FeII system under oxic conditions. The findings are crucial to comprehensively understand and predict the behavior of FeII and AsV with coexisting engineering black carbon in natural environments.
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Conjugated polymers promise inherently flexible and low-cost thermoelectrics for powering the Internet of Things from waste heat1,2. Their valuable applications, however, have been hitherto hindered by the low dimensionless figure of merit (ZT)3-6. Here we report high-ZT thermoelectric plastics, which were achieved by creating a polymeric multi-heterojunction with periodic dual-heterojunction features, where each period is composed of two polymers with a sub-ten-nanometre layered heterojunction structure and an interpenetrating bulk-heterojunction interface. This geometry produces significantly enhanced interfacial phonon-like scattering while maintaining efficient charge transport. We observed a significant suppression of thermal conductivity by over 60 per cent and an enhanced power factor when compared with individual polymers, resulting in a ZT of up to 1.28 at 368 kelvin. This polymeric thermoelectric performance surpasses that of commercial thermoelectric materials and existing flexible thermoelectric candidates. Importantly, we demonstrated the compatibility of the polymeric multi-heterojunction structure with solution coating techniques for satisfying the demand for large-area plastic thermoelectrics, which paves the way for polymeric multi-heterojunctions towards cost-effective wearable thermoelectric technologies.
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Psoriasis is a common inflammatory skin disorder with no cure. Mesenchymal stem cells (MSCs) have immunomodulatory properties for psoriasis, but the therapeutic efficacies varied, and the molecular mechanisms were unknown. In this study, we improved the efficacy by enhancing the immunomodulatory effects of umbilical cord-derived MSCs (UC-MSCs). UC-MSCs stimulated by TNF-α and IFN-γ exhibited a better therapeutic effect in a mouse model of psoriasis. Single-cell RNA sequencing revealed that the stimulated UC-MSCs overrepresented a subpopulation expressing high tryptophanyl-tRNA synthetase 1 (WARS1). WARS1-overexpressed UC-MSCs treat psoriasis-like skin inflammation more efficiently than control UC-MSCs by restraining the proinflammatory macrophages. Mechanistically, WARS1 maintained a RhoA-Akt axis and governed the immunomodulatory properties of UC-MSCs. Together, we identify WARS1 as a master regulator of UC-MSCs with enhanced immunomodulatory capacities, which paves the way for the directed modification of UC-MSCs for escalated therapeutic efficacy.
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Imunomodulação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Animais , Camundongos , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Triptofano-tRNA Ligase/genética , Psoríase/imunologia , Psoríase/terapia , Modelos Animais de Doenças , Análise de Célula Única , Análise de Sequência de RNA , Cordão Umbilical/citologia , Cordão Umbilical/imunologia , Camundongos Endogâmicos C57BL , Células CultivadasRESUMO
Due to the unsatisfactory mechanical properties of natural polymer-based conductive hydrogels, their applications are limited. Shaanxi Biangbiang noodles can be toughened by applying external mechanical forces through stretching and beating movements; this process provides inspiration for the preparation of high-strength hydrogels. In this paper, we propose a strategy for the preparation of ultrastrong and ultratough conductive hydrogels by directional prestretching and solvent exchange. Neatly arranged fiber bundles containing many intermolecular hydrogen bonds and metal ion coordination bonds are successfully constructed inside the prepared hydrogels. The hydrogel has exceptional mechanical properties, with a fracture stress exceeding 50 MPa, fracture strain approaching 105 %, fracture toughness exceeding 30 MJ m-3, and high conductivity reaching 11.738 ± 0.06 mS m-1. Impressively, the hydrogel can maintain its high mechanical properties after being frozen at an ultralow temperature of -80 °C for 7 days. Compared with other tough hydrogels, natural tendons and synthetic rubbers, the hydrogel exhibits excellent mechanical properties. The cellulose-based conductive hydrogel prepared in this study can be applied to robotic soft tissues (such as the Achilles tendon) that require high strength and are operated in extreme environments.
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Advancing iontronics with precisely controlled ion transport is fundamentally important to bridge external organic electronics with the biosystem. This long-standing goal, however, is thus far limited by the trade-off between the active ion electromigration and idle diffusion leakage in the (semi)crystalline film. Here, we presented a mixed-orientation strategy by blending a conjugated polymer, allowing for simultaneously high ion electromigration efficiency and low leakage. Our studies revealed that edge-on aggregation with a significant percolative pathway exhibits much higher ion permeability than that of the face-on counterpart but encounters pronounced leakage diffusion. Through carefully engineering the mixed orientations, the polymer composite demonstrated an ideal switchable ion-transport behavior, achieving a remarkably high electromigration efficiency exceeding one quadrillion ions per milliliter per minute and negligible idle leakage. This proof of concept, validated by drug release in a skin-conformable organic electronic ion pump (OEIP), offers a rational approach for the development of multifunctional iontronic devices.
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The nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway represents a crucial intrinsic protective system against oxidative stress and inflammation and plays a significant role in various neurological disorders. However, the effect of Nrf2 signalling on the regulation of cognitive impairment remains unknown. Dexmedetomidine (DEX) has neuroprotective effects and can ameliorate lipopolysaccharide (LPS)-induced cognitive dysfunction. Our objective was to observe whether Nrf2 knockout influences the efficacy of DEX in improving cognitive impairment and to attempt to understand its underlying mechanisms. An LPS-induced cognitive dysfunction model in wild-type and Nrf2 knockout mice (Institute of Cancer Research background; male; 8-12 weeks) was used to observe the impact of DEX on cognitive dysfunction. LPS was intraperitoneally injected, followed by novel object recognition and morris water maze experiments 24â¯h later. Hippocampal tissues were collected for histopathological and molecular analyses. Our research findings suggest that DEX enhances the expression of NQO1, HO-1, PSD95, and SYP proteins in hippocampal tissue, inhibits microglial proliferation, reduces pro-inflammatory cytokines IL-1ß and TNF-É, increases anti-inflammatory cytokine IL-10, and improves dendritic spine density, thereby alleviating cognitive dysfunction induced by LPS. However, the knockout of the Nrf2 gene negated the aforementioned effects of DEX. In conclusion, DEX alleviates cognitive deficits induced by LPS through mechanisms of anti-oxidative stress and anti-inflammation, as well as by increasing synaptic protein expression and dendritic spine density. However, the knockout of the Nrf2 gene reversed the effects of DEX. The Nrf2 signaling pathway plays a crucial role in the mitigation of LPS-induced cognitive impairment by DEX.
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Disfunção Cognitiva , Dexmedetomidina , Modelos Animais de Doenças , Hipocampo , Lipopolissacarídeos , Camundongos Knockout , Fator 2 Relacionado a NF-E2 , Fármacos Neuroprotetores , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Dexmedetomidina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/induzido quimicamente , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Camundongos , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Lipopolissacarídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
PURPOSE: To explore the mediating effect of hope in the relationships between social support and self-esteem with psychological resilience among patients with stroke survivors in early rehabilitation. METHODS: A cross-sectional study design was adopted. Data from a cross-sectional survey of 210 patients undergoing early stroke rehabilitation were analyzed using structural equation modeling. The variables of interest were measured using the Connor Davidson Resilience Scale, the Social Support Rating Scale, the Herth Hope Index, and the Self-Esteem Scale. This article reports according to the STROBE checklist. RESULTS: A positive relationship was found between social support and psychological resilience (ß1 = 0.548), which was mediated by hope (ß2 = 0.114), and social support had significant direct effect on resilience (ß3 = 0.434). A positive relationship was also found between self-esteem and psychological resilience (ß4 = 0.380), which was mediated by hope (ß5 = 0.200), and self-esteem had significant direct effect on resilience (ß6 = 0.179). CONCLUSION: According to the results of this study, some strategies can be incorporated into the rehabilitation process to enhance psychological resilience, such as cultivating individual personality characteristics and improving patients' social relationships. In the future, we need to explore methods for improving psychological resilience among patients with stroke in combination with their risk factors to improve their quality of life and reduce the incidence of post-stroke depression.
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Esperança , Resiliência Psicológica , Autoimagem , Apoio Social , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Idoso , Acidente Vascular Cerebral/psicologia , Reabilitação do Acidente Vascular Cerebral/psicologia , AdultoRESUMO
Soil organic matter (SOM) and clay minerals are important sinks for reactive heavy metals (HMs) and exogenous hydrogen ions (H+). Therefore, HMs are likely to be released into soil porewater under acid rainfall conditions due to the competitive adsorption of H+. However, negligible Lead, Zinc, and Cadmium (<6 ) in the Pb/Zn smelter soil were leached, and the effects of SOM and clay minerals on HMs leaching were unclear. Herein, the H+ consumption and HMs redistribution on SOM and clay minerals were quantitated by the multi-surface model and density functional theory calculations to reveal the roles of SOM and clay minerals in alleviating HMs' leaching. Clay minerals consumed 43.2 %-52.0 % of the exogenous H+, serving as the dominant sink for the exogenous H+ due to its high content and hindering H+ competitive adsorption on SOM. Protonation of the functional groups constituted >90 % of the total H+ captured by clay minerals. Meanwhile, some H+ also competed with HMs for adsorption sites on clay minerals due to its 0.497-fold to 1.54-fold higher binding energies than HMs, resulting in the release of HMs. On the contrary, SOM served as an accommodator for taking over the released HMs from clay minerals. The HMs complexation on the low-affinity sites (R-L-) of SOM was responsible for the recapture of HMs. In Ca-enriched soil, the released HMs were also recaptured by SOM via ion exchange on the R-L-Ca+ and the high-affinity sites (R-H-Ca+) sites due to the 30.8 %-178 % higher binding energies of HMs on these sites than those of Ca. As a result, >63.4 % of the released HMs from clay minerals were transferred to the SOM. Thus, the synergy of SOM and clay minerals in alleviating the leaching of HMs in Pb/Zn smelter soils cannot be ignored in risk assessment and soil remediation.
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Chimeric antigen receptor (CAR) T cells have demonstrated outstanding therapeutic success in hematological malignancies. Yet, their efficacy against solid tumors remains constrained due to inadequate infiltration of cytotoxic T and CAR-T cells in the tumor microenvironment (TME), a factor correlated with poor prognosis in patients with solid tumors. To overcome this limitation, we engineered CAR-T cells to secrete CXCL10 and IL15 (10 × 15 CAR-T), which sustain T cell viability and enhance their recruitment, thereby amplifying the long-term cytotoxic capacity of CAR-T cells in vitro. In a xenograft model employing NUGC4-T21 cells, mice receiving 10 × 15 CAR-T cells showed superior tumor reduction and extended survival rates compared to those treated with second-generation CAR-T cells. Histopathological evaluations indicated a pronounced increase in cytotoxic T cell accumulation in the TME post 10 × 15 CAR-T cell treatment. Therefore, the synergistic secretion of CXCL10 and IL15 in these CAR-T cells enhances T cell recruitment and adaptability within tumor tissues, improving tumor control. This approach may offer a promising strategy for advancing CAR-T therapies in the treatment of solid tumors.
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Quimiocina CXCL10 , Imunoterapia Adotiva , Interleucina-15 , Receptores de Antígenos Quiméricos , Neoplasias Gástricas , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Neoplasias Gástricas/terapia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/genética , Humanos , Camundongos , Interleucina-15/genética , Interleucina-15/metabolismo , Imunoterapia Adotiva/métodos , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Linfócitos T Citotóxicos/imunologia , Sobrevivência Celular , FemininoRESUMO
Introduction: Peripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear. Methods: In this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients. Results: Covariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (ß = -0.27, p = 0.003) and the putamen (ß = -0.27, p = 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: ß = -0.37, p = 0.013; putamen: ß = -0.45, p = 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25, p = 0.013; putamen: ρ = 0.22, p = 0.026) or in the early-stage subgroup (caudate: ρ = 0.31, p = 0.023, putamen: ρ = 0.34, p = 0.011). Conclusion: Dopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.
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BACKGROUND: As the major protein (approximately 36%) in rice bran, globulin exhibits excellent foaming and emulsifying properties, endowing its useful application as a foaming and emulsifying agent in the food industry. However, the low water solubility restricts its commercial potential in industrial applications. The present study aimed to improve this protein's processing and functional properties. RESULTS: A novel covalent complex was fabricated by a combination of the Maillard reaction and alkaline oxidation using rice bran globulin (RBG), chitooligosaccharide (C), quercetin (Que) and resveratrol (Res). The Maillard reaction improved the solubility, emulsifying and foaming properties of RBG. The resultant glycosylated protein was covalently bonded with quercetin and resveratrol to form a (RBG-C)-Que-Res complex. (RBG-C)-Que-Res exhibited higher thermal stability and antioxidant ability than the native protein, binary globulin-chitooligosaccharide or ternary globulin-chitooligosaccharide-polyphenol (only containing quercetin or resveratrol) conjugates. (RBG-C)-Que-Res exerted better cytoprotection against the generation of malondialdehyde and reactive oxygen species in HepG2 cells, which was associated with increased activities of antioxidative enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) through upregulated genes SOD1, CAT, GPX1 (i.e. gene for glutathione peroxidase-1), GCLM (i.e. gene for glutamate cysteine ligase modifier subunit), SLC1A11 (i.e. gene for solute carrier family 7, member 11) and SRXN1 (i.e. gene for sulfiredoxin-1). The anti-apoptotic effect of (RBG-C)-Que-Res was confirmed by the downregulation of caspase-3 and p53 and the upregulation of B-cell lymphoma-2 gene expression. CONCLUSION: The present study highlights the potential of (RBG-C)-Que-Res conjugates as functional ingredients in healthy foods. © 2024 Society of Chemical Industry.
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Antioxidantes , Quitosana , Oligossacarídeos , Oryza , Quercetina , Resveratrol , Humanos , Quercetina/química , Quercetina/análogos & derivados , Oryza/química , Oligossacarídeos/química , Resveratrol/química , Resveratrol/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Quitosana/química , Células Hep G2 , Quitina/química , Quitina/análogos & derivados , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Reação de Maillard , Catalase/metabolismo , Catalase/genética , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/genéticaRESUMO
AIMS/INTRODUCTION: Tanshinone IIA (TIIA) is one of the main components of the root of the red-rooted Salvia miltiorrhiza Bunge. However, the molecular mechanisms underlying TIIA-mediated protective effects in diabetic nephropathy (DN) are still unclear. MATERIALS AND METHODS: High glucose (HG)-induced mouse podocyte cell line (MPC5) cells were used as the in vitro model of DN and treated with TIIA. Cell viability, proliferation and apoptosis were detected using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, 5-ethynyl-2'-deoxyuridine and flow cytometry assays. The protein levels were assessed using western blot assay. The levels of inflammatory factors were deleted by enzyme-linked immunoassay. Fe+ level, reactive oxygen species, malondialdehyde and glutathione products were detected using special assay kits. After ENCORI prediction, the interaction between embryonic lethal abnormal visual-like protein 1 (ELAVL1) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) was verified using co-immunoprecipitation assay and dual-luciferase reporter assays. ACSL4 messenger ribonucleic acid expression was measured using real-time quantitative polymerase chain reaction. RESULTS: TIIA repressed HG-induced MPC5 cell apoptosis, inflammatory response and ferroptosis. ACSL4 upregulation relieved the repression of TIIA on HG-mediated MPC5 cell injury and ferroptosis. ELAVL1 is bound with ACSL4 to positively regulate the stability of ACSL4 messenger ribonucleic acid. TIIA hindered HG-triggered MPC5 cell injury and ferroptosis by regulating the ELAVL1-ACSL4 pathway. TIIA blocked DN progression in in vivo research. CONCLUSION: TIIA treatment restrained HG-caused MPC5 cell injury and ferroptosis partly through targeting the ELAVL1-ACSL4 axis, providing a promising therapeutic target for DN treatment.
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Abietanos , Coenzima A Ligases , Nefropatias Diabéticas , Ferroptose , Podócitos , Transdução de Sinais , Abietanos/farmacologia , Ferroptose/efeitos dos fármacos , Animais , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Podócitos/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Coenzima A Ligases/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Apoptose/efeitos dos fármacos , Linhagem CelularRESUMO
The musculoskeletal system, constituting the largest human physiological system, plays a critical role in providing structural support to the body, facilitating intricate movements, and safeguarding internal organs. By virtue of advancements in revolutionized materials and devices, particularly in the realms of motion capture, health monitoring, and postoperative rehabilitation, "musculoskeletal electronics" has actually emerged as an infancy area, but has not yet been explicitly proposed. In this review, the concept of musculoskeletal electronics is elucidated, and the evolution history, representative progress, and key strategies of the involved materials and state-of-the-art devices are summarized. Therefore, the fundamentals of musculoskeletal electronics and key functionality categories are introduced. Subsequently, recent advances in musculoskeletal electronics are presented from the perspectives of "in vitro" to "in vivo" signal detection, interactive modulation, and therapeutic interventions for healing and recovery. Additionally, nine strategy avenues for the development of advanced musculoskeletal electronic materials and devices are proposed. Finally, concise summaries and perspectives are proposed to highlight the directions that deserve focused attention in this booming field.
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Dispositivos Eletrônicos Vestíveis , Humanos , Sistema Musculoesquelético , EletrônicaRESUMO
Nanoresolved doping of polymeric semiconductors can overcome scaling limitations to create highly integrated flexible electronics, but remains a fundamental challenge due to isotropic diffusion of the dopants. Here we report a general methodology for achieving nanoscale ion-implantation-like electrochemical doping of polymeric semiconductors. This approach involves confining counterion electromigration within a glassy electrolyte composed of room-temperature ionic liquids and high-glass-transition-temperature insulating polymers. By precisely adjusting the electrolyte glass transition temperature (Tg) and the operating temperature (T), we create a highly localized electric field distribution and achieve anisotropic ion migration that is nearly vertical to the nanotip electrodes. The confined doping produces an excellent resolution of 56 nm with a lateral-extended doping length down to as little as 9.3 nm. We reveal a universal exponential dependence of the doping resolution on the temperature difference (Tg - T) that can be used to depict the doping resolution for almost infinite polymeric semiconductors. Moreover, we demonstrate its implications in a range of polymer electronic devices, including a 200% performance-enhanced organic transistor and a lateral p-n diode with seamless junction widths of <100 nm. Combined with a further demonstration in the scalability of the nanoscale doping, this concept may open up new opportunities for polymer-based nanoelectronics.
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Polymer semiconductors hold tremendous potential for applications in flexible devices, which is however hindered by the fact that they are usually processed by halogenated solvents rather than environmentally more friendly solvents. An effective strategy to boost the solubility of high-performance polymer semiconductors in nonhalogenated solvents such as tetrahydrofuran (THF) by appending hydroxyl groups in the side chains is herein presented. The results show that hydroxyl groups, which can be easily incorporated into the side chains, can significantly improve the solubility of typical p- and n-types as well as ambipolar polymer semiconductors in THF. Meanwhile, the thin films of these polymer semiconductors from the respective THF solutions show high charge mobilities. With THF as the processing and developing solvents these polymer semiconductors with hydroxyl groups in the side chains can be well photopatterned in the presence of the photo-crosslinker, and the charge mobilities of the patterned thin films are mostly maintained by comparing with those of the respective pristine thin films. Notably, THF is successfully utilized as the processing and developing solvent to achieve high-density photopatterning with ≈82 000 device arrays cm-2 for polymer semiconductors in which hydroxyl groups are appended in the side chains.
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BACKGROUND: The goal of anesthesia in patients with hypertrophic obstructive cardiomyopathy (HOCM) is to reduce the risk of left ventricular outflow tract obstruction triggered by anesthetics. Remimazolam is a newly developed anesthetic that has been reported to have superior hemodynamic stability. There have been no reports on the completion of non-cardiac surgery with remimazolam in patients with HOCM. METHODS: Here we report the case of a 49-year-old man diagnosed with hypertrophic obstructive cardiomyopathy who underwent resection of colon cancer with remimazolam and remifentanil anesthesia. A bolus 0.3 mg/kg remimazolam was administered for anesthesia induction, and then adjusted to 2 mg/kg/h to maintain anesthesia. Set the pain threshold index to 50 to auto-control the infusion speed of remifentanil. RESULTS: No hypotension occurred during anesthesia, and norepinephrine was not administered. After conversion to open surgery, the patient's blood pressure elevated and reduced with urapidil and esmolol. CONCLUSION: In this patient with HOCM, remimazolam and remifentanil provided adequate anesthesia for induction and maintenance to complete the right hemicolectomy.
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Anestésicos , Benzodiazepinas , Cardiomiopatia Hipertrófica , Neoplasias Colorretais , Masculino , Humanos , Pessoa de Meia-Idade , Remifentanil , Anestesia Geral , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/cirurgia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgiaRESUMO
Heat shock transcription factors (HSFs) are an essential plant-specific transcription factor family that regulates the developmental and growth stages of plants, their signal transduction, and their response to different abiotic and biotic stresses. The HSF gene family has been characterized and systematically observed in various species; however, research on its association with Lycoris radiata is limited. This study identified 22 HSF genes (LrHSFs) in the transcriptome-sequencing data of L. radiata and categorized them into three classes including HSFA, HSFB, and HSFC, comprising 10, 8, and 4 genes, respectively. This research comprises basic bioinformatics analyses, such as protein sequence length, molecular weight, and the identification of its conserved motifs. According to the subcellular localization assessment, most LrHSFs were present in the nucleus. Furthermore, the LrHSF gene expression in various tissues, flower developmental stages, two hormones stress, and under four different abiotic stresses were characterized. The data indicated that LrHSF genes, especially LrHSF5, were essentially involved in L. radiata development and its response to different abiotic and hormone stresses. The gene-gene interaction network analysis revealed the presence of synergistic effects between various LrHSF genes' responses against abiotic stresses. In conclusion, these results provided crucial data for further functional analyses of LrHSF genes, which could help successful molecular breeding in L. radiata.