RESUMO
OBJECTIVE: Dementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous. METHODS: This study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO2), nitrogen oxides (NOX), particulate matter (PM2.5, PM10, and PMcoarse) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales. RESULTS: During a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standarddeviationincrease in ambient NO2, NOX or PM2.5, all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO2, NOX or PM2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer's disease (AD), but no significant modification effects are found for sleep patterns or smoking status. CONCLUSION: The increased exposures of NO2, NOX, or PM2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings.
RESUMO
Poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) are extensively studied biodegradable polymers. However, the degradation behavior of their copolymer, poly(lactic-co-glycolic acid) (PLGA), in marine environments has not yet been confirmed. In this study, the changes in macroscopic and microscopic morphology, thermal properties, aggregation, and chemical structure of PLA, PGA, PLGA-85, and PLGA-75 (with 85% and 75% LA content) in simulated marine environments were investigated. Results revealed that degradation occurred through hydrolysis of ester bonds, and the degradation rate of PGA was faster than that of PLA. The amorphous region degraded preferentially over the crystalline region, leading to cleavage-induced crystallization and decreased thermal stability of PLA, PLGA-85, and PLGA-75. The crystal structures of PLGAs were similar to those of PLA, and the higher GA content, the faster was the degradation rate. This study provides a deeper understanding of the seawater degradation behaviors of PLA, PGA, and their copolymers, and provides guidance for the preparation of materials with controllable degradation performance.
RESUMO
Tissue engineering has emerged as an advanced strategy to regenerate various tissues using different raw materials, and thus it is desired to develop more approaches to fabricate tissue engineering scaffolds to fit specific yet very useful raw materials such as biodegradable aliphatic polyester like poly (lactide-co-glycolide) (PLGA). Herein, a technique of 'wet 3D printing' was developed based on a pneumatic extrusion three-dimensional (3D) printer after we introduced a solidification bath into a 3D printing system to fabricate porous scaffolds. The room-temperature deposition modeling of polymeric solutions enabled by our wet 3D printing method is particularly meaningful for aliphatic polyester, which otherwise degrades at high temperature in classic fuse deposition modeling. As demonstration, we fabricated a bilayered porous scaffold consisted of PLGA and its mixture with hydroxyapatite for regeneration of articular cartilage and subchondral bone. Long-termin vitroandin vivodegradation tests of the scaffolds were carried out up to 36 weeks, which support the three-stage degradation process of the polyester porous scaffold and suggest faster degradationin vivothanin vitro. Animal experiments in a rabbit model of articular cartilage injury were conducted. The efficacy of the scaffolds in cartilage regeneration was verified through histological analysis, micro-computed tomography (CT) and biomechanical tests, and the influence of scaffold structures (bilayerversussingle layer) onin vivotissue regeneration was examined. This study has illustrated that the wet 3D printing is an alternative approach to biofabricate tissue engineering porous scaffolds based on biodegradable polymers.
Assuntos
Cartilagem Articular , Animais , Coelhos , Porosidade , Microtomografia por Raio-X , Temperatura , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Polímeros , Poliésteres , Impressão TridimensionalRESUMO
The shortage of freshwater resources is a serious problem faced by mankind in the 21st century. To maximize the acquisition of freshwater resources, numerous fog collectors have been constructed. In the process of fog collection accompanied by the movement of the wind, the mechanical energy brought about by the wind is often ignored. Based on this, inspired by beetles and origami art, we designed a windmill installation with a bump on the edge. Droplets nucleate at the windmill bulge and accelerate the transport process under the action of centrifugal force. This leads to quick fog collection and reduces the secondary evaporation rate of freshwater resources. The fog collection efficiency can reach 2.8 times that of the original sample. Moreover, the windmill can convert mechanical energy into electricity while collecting fog, and the operating voltage of a single windmill can reach 0.85 V. After the array, the amount of fog collected by the windmill and the power generation voltage can be increased by multiple times, which realizes the efficient use of energy and provides a new idea for the design of an efficient fog collector in the future.
RESUMO
Heavy metal exposure is a known risk factor for hematologic disorders in children, yet the impact of co-exposure to multiple metals remains underexplored. This cross-sectional study investigates the relationship between urinary levels of 23 metals and haemoglobin (Hb) in 1460 Chinese preschoolers. The concentrations of the 23 urinary metals were quantified using an inductively coupled plasma mass spectrometer, while Hb levels were assessed through finger prick blood samples. To evaluate the co-exposure effects, we employed three approaches: Generalized linear regression model, joint effect models including Quantile g-Computation and Bayesian Kernel Machine Regression (BKMR). From the generalized linear regression and Quantile g-computation, urinary uranium, thallium, aluminium, iron and tungsten were correlated negatively with Hb, while urinary barium was correlated positively (all P < 0.05). Moreover, significant negative associations between metal mixtures exposure with Hb were identified in both Quantile g-computation [ß (95% CI): -0.083 (-0.132, -0.033), P = 0.0012] and BKMR [90th percentile vs. 50th percentile ß (95% CI): -0.238 (-0.368, -0.107), P < 0.001] with aluminium emerging as the primary contributor to this joint effect (weight in Quantile g-computation = 0.399, PIPs in BKMR = 0.896). These findings provide a potential explanation for environmental exposure to metals and Hb-related disease in preschoolers.
Assuntos
Hemoglobinas , Humanos , Pré-Escolar , Masculino , Feminino , Hemoglobinas/análise , Hemoglobinas/metabolismo , Estudos Transversais , China , Metais Pesados/urina , Metais Pesados/sangue , Metais/urina , Metais/sangue , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , População do Leste AsiáticoRESUMO
As endoscopic imaging technology advances, there is a growing clinical demand for enhanced imaging capabilities. Although conventional white light imaging (WLI) endoscopy offers realistic images, it often cannot reveal detailed characteristics of the mucosa. On the other hand, optical staining endoscopy, such as Compound Band Imaging (CBI), can discern subtle structures, serving to some extent as an optical biopsy. However, its image brightness is low, and the colors can be abrupt. These two techniques, commonly used in clinical settings, have complementary advantages. Nonetheless, they require different lighting conditions, which makes it challenging to combine their imaging strengths on living tissues. In this study, we introduce a novel endoscopic imaging technique that effectively combines the advantages of both WLI and CBI. Doctors don't need to manually switch between these two observation modes, as they can obtain the image information of both modes in one image. We calibrated an appropriate proportion for simultaneous illumination with the light required for WLI and CBI. We designed a new illumination spectrum tailored for gastrointestinal examination, achieving their fusion at the optical level. Using a new algorithm that focuses on enhancing specific hemoglobin tissue features, we restored narrow-band image characteristics lost due to the introduction of white light. Our hardware and software innovations not only boost the illumination brightness of the endoscope but also ensure the narrow-band feature details of the image. To evaluate the reliability and safety of the new endoscopic system, we conducted a series of tests in line with relevant international standards and validated the design parameters. For clinical trials, we collected a total of 256 sets of images, each set comprising images of the same lesion location captured using WLI, CBI, and our proposed method. We recruited four experienced clinicians to conduct subjective evaluations of the collected images. The results affirmed the significant advantages of our method. We believe that the novel endoscopic system we introduced has vast potential for clinical application in the future.
RESUMO
Epidemiologic studies have reported the positive relationship of benzo[a]pyrene (BaP) exposure with the risk of lung cancer. However, the mechanisms underlying the relationship is still unclear. Plasma microRNA (miRNA) is a typical epigenetic biomarker that was linked to environment exposure and lung cancer development. We aimed to reveal the mediation effect of plasma miRNAs on BaP-related lung cancer. We designed a lung cancer case-control study including 136 lung cancer patients and 136 controls, and measured the adducts of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) and sequenced miRNA profiles in plasma. The relationships between BPDE-Alb adducts, normalized miRNA levels and the risk of lung cancer were assessed by linear regression models. The mediation effects of miRNAs on BaP-related lung cancer were investigated. A total of 190 plasma miRNAs were significantly related to lung cancer status at Bonferroni adjusted P < 0.05, among which 57 miRNAs showed different levels with |fold change| > 2 between plasma samples before and after tumor resection surgery at Bonferroni adjusted P < 0.05. Especially, among the 57 lung cancer-associated miRNAs, BPDE-Alb adducts were significantly related to miR-17-3p, miR-20a-3p, miR-135a-5p, miR-374a-5p, miR-374b-5p, miR-423-5p and miR-664a-5p, which could in turn mediate a separate 42.2%, 33.0%, 57.5%, 36.4%, 48.8%, 32.5% and 38.2% of the relationship of BPDE-Alb adducts with the risk of lung cancer. Our results provide non-invasion biomarker candidates for lung cancer, and highlight miRNAs dysregulation as a potential intermediate mechanism by which BaP exposure lead to lung tumorigenesis.
Assuntos
Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/genética , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Benzo(a)pireno/toxicidade , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Estudos de Casos e Controles , Pulmão , Biomarcadores , ChinaRESUMO
PURPOSE: White light imaging (WLI) is a commonly seen examination mode in endoscopy. The particular light in compound band imaging (CBI) can highlight delicate structures, such as capillaries and tiny structures on the mucosal surface. These two modes complement each other, and doctors switch between them manually to complete the examination. This paper proposes an endoscopy image fusion system to combine WLI and CBI. METHODS: We add a real-time rotatable color wheel in the light source device of the AQ-200 endoscopy system to achieve rapid imaging of two modes at the same position of living tissue. The two images corresponding to the pixel level can avoid registration and lay the foundation for image fusion. We propose a multi-scale image fusion framework, which involves Laplacian pyramid (LP) and convolutional sparse representation (CSR) and strengthens the details in the fusion rule. RESULTS: Volunteer experiments and ex vivo pig stomach trials are conducted to verify the feasibility of our proposed system. We also conduct comparative experiments with other image fusion methods, evaluate the quality of the fused images, and verify the effectiveness of our fusion framework. The results show that our fused image has rich details, high color contrast, apparent structures, and clear lesion boundaries. CONCLUSION: An endoscopy image fusion system is proposed, which does not change the doctor's operation and makes the fusion of WLI and CBI optical staining technology a reality. We change the light source device of the endoscope, propose an image fusion framework, and verify the feasibility and effectiveness of our scheme. Our method fully integrates the advantages of WLI and CBI, which can help doctors make more accurate judgments than before. The endoscopy image fusion system is of great significance for improving the detection rate of early lesions and has broad application prospects.
Assuntos
Endoscopia Gastrointestinal , Endoscopia , Humanos , Animais , Suínos , Luz , Imagem de Banda Estreita/métodosRESUMO
A plethora of research has focused on the biosafety of biodegradable plastics (BPs), including their microplastic formation and additives leaching; however, relatively fewer studies have explored biodegradation products. This study aims to investigate the biological effects and chemical features of degradation products from three kinds of BPs, namely polyglycolic acid (PGA), poly (butylene adipate-co-terephthalate) (PBAT), and the blends of PGA/PBAT without the addition of additives, in a simulated small waterbody environment with extracted soil solution for three months. Results showed that exposure to the whole degradation remnants of three BPs had no lethal effects on zebrafish at the current BP environmental concentrations (from 0.24 to 12.72 mg plastic/L) in small waterbodies. However, from the calculated BPs environmental concentrations (from 0.57 to 43.82 mg plastic/L) in 2026, PGA and PGA/PBAT blends may cause adverse effects on the cardiovascular system such as heartbeat rate suppression in zebrafish embryos, and also lead to reduced body length and pericardial edema and spinal curvature in fish larvae. We further qualitatively analyzed the composition of degradation products, and quantitatively measured four dominant degradation monomers (glycolic acid (GA), adipic acid (A), 1,4-butanediol (B), and terephthalic acid (T)) in the degradation remnants. It was found that the observed toxicities were probably due to the presence of GA, A, and T monomers, and their concentrations can reach 0.776, 0.034, and 0.6 mg/L under the calculated future scenario, respectively. It is worth mentioning that either GA or T monomers at the above concentrations were found to cause suppressed heartbeat rate in zebrafish embryos. Collectively, though the degradation products of BPs are temporarily safe at current environmental concentrations, they may lead to non-negligible toxicity with increasing production and continual improper recycling and/or BP waste management.
Assuntos
Plásticos Biodegradáveis , Animais , Plásticos/toxicidade , Poliésteres/química , Peixe-Zebra , Biodegradação Ambiental , MicroplásticosRESUMO
Collecting water in fog has also become a breakthrough to solve the hidden danger of water shortage in some arid areas. The three-dimensional (3D) structure fog collection material can increase the surface area in direct contact with the fog flow and reduce the quick flow of fog, which can effectively improve the fog collection efficiency. Imitating the three-dimensional structure of corrugated paper, the 3D fog collecting material with hybrid wettability was prepared by chemical and physical means. We discuss the influence of different wettability combinations on the fog collection efficiency of 3D structures and study the influence of spraying times and illumination times on the surface wettability during the construction of wettability. We also study the influence of the concavity and tip as well as the bending angle on the fog collection in the 3D structure and obtain the most reasonable concavity and convex ratio and bending angle. The superhydrophilic and superhydrophobic 3D structure fog harvesting material prepared by us performs well in the fog harvesting process, and the fog harvesting efficiency reaches 1.442 g cm-2 h-1. The fog collection efficiency is 418% of the original zinc sheet. At the same time, compared with the superhydrophilic and superhydrophobic hybrid two-dimensional (2D) plane, the increase is 168%, and compared with the superhydrophobic 3D structure, the increase is 150%.
RESUMO
OBJECTIVE: This study aimed to investigate the factors influencing Procalcitonin (PCT) in the cerebrospinal fluid (CSF) of patients with high fever and suspected intracranial infection after neurosurgery and its clinical application value. METHODS: Between February 2021 and August 2022, CSF and serum samples were collected via lumbar puncture from patients with high fever and suspected intracranial infection in the Intensive Care Unit(ICU) of our hospital. Multivariate logistic regression analysis was performed to analyze the factors influencing elevated PCT in CSF. The diagnostic efficacy of each index was assessed using receiver operating characteristic (ROC) curves. RESULTS: A total of 183 CSF samples were collected, of which 148 had increased PCT levels, including 73 cases of intracranial infection and 75 cases in the caseâcontrol group. Multivariate logistic regression analysis showed that intracranial infection [OR = 0.117, 95% CI: 0.025-0.559; p < 0.01] and hemorrhagic CSF [OR = 0.162, 95% CI: 0.029-0.916; p < 0.04] were factors influencing CSF PCT, while trauma [OR = 3.43, 95% CI: 0.76-15.45; p < 0.12], epileptic seizure [OR = 0.00, 95% CI: 0.00; p < 0], age [OR = 1.02, 95% CI: 0.98-1.52; p < 0.32] and Glasgow Coma Scale (GCS) score [OR = 1.03, 95% CI: 0.78-1.32; p < 0.83] did not influence CSF PCT. The CSF PCT and serum PCT levels in the intracranial infection group and the caseâcontrol group were 0.13 (0.11, 0.25) ng/ml and 0.14 (0.07, 0.25) ng/ml and 0.14 (0.08,0.32) ng/ml and 0.23 (0.13,0.48)ng/ml, respectively, with no statistically significant difference. The median values of CSF lactate in the intracranial infection group and the caseâcontrol group were 6.45 (4.475, 8.325) mmol/l and 3.2 (2.02, 4.200) mmol/l, respectively, with a statistically significant difference between the groups.The areas under the ROC curve of CSF PCT, serum PCT,CSF lactate, CSF PCT combined with lactate were 0.59, 0.63, 0.82,and 0.83,respectively. CONCLUSION: Intracranial infection and hemorrhagic CSF are influencing factors for elevated CSF PCT following neurosurgery. It should be noted that the diagnostic value of intracranial infection by CSF PCT elevated alone is limited, but the combination it with other indicators can help improve diagnostic efficacy.
Assuntos
Neurocirurgia , Pró-Calcitonina , Humanos , Curva ROC , Procedimentos Neurocirúrgicos , Ácido Láctico , Prognóstico , Estudos RetrospectivosRESUMO
Expanded polytetrafluoroethylene (ePTFE) is promising in biomedical fields such as covered stents and plastic surgery owing to its excellent biocompatibility and mechanical properties. However, ePTFE material prepared by the traditional biaxial stretching process is with thicker middle and thinner sides due to the bowing effect, which poses a major problem in industrial-scale fabrication. To solve this problem, we design an olive-shaped winding roller to provide the middle part of the ePTFE tape with a greater longitudinal stretching amplitude than the two sides, so as to make up for the excessive longitudinal retraction tendency of the middle part when it is transversely stretched. The as-fabricated ePTFE membrane has, as designed, uniform thickness and node-fibril microstructure. In addition, we examine the effects of mass ratio of lubricant to PTFE powder, biaxial stretching ratio and sintering temperature on the performance of the resultant ePTFE membranes. Particularly, the relation between the internal microstructure of the ePTFE membrane and its mechanical properties is revealed. Besides stable mechanical properties, the sintered ePTFE membrane exhibits satisfactory biological properties. We make a series of biological assessments including in vitro hemolysis, coagulation, bacterial reverse mutation and in vivo thrombosis, intracutaneous reactivity test, pyrogen test and subchronic systemic toxicity test; all of the results meet the relevant international standards. The muscle implantation of the sintered ePTFE membrane into rabbits indicates acceptable inflammatory reactions of our sintered ePTFE membrane fabricated on industrial scale. Such a medical-grade raw material with the unique physical form and condensed-state microstructure is expected to afford an inert biomaterial potentially for stent-graft membrane.
RESUMO
By collecting water in the air, it is an important way to solve the problem of water shortage in arid and semi-arid areas. Improving the efficiency of fog harvesting is still a great challenge to be overcome. The use of 3D structure is an excellent strategy, here, a Multiple-biomimetic 3D hydrophilic and superhydrophobic fog harvester with a hump-valley structure was prepared by the combination of thermal processing and spraying. Inspired by biological water collection in nature, a 3D porous sponge surface with hydrophilic valley and superhydrophobic hump was obtained by two-step treatment. This surface structure showed excellent fog harvesting performance, which was 185 % higher than the original sponge. This structure accelerates the capture, transfer and transport of droplets during the fog harvesting process and greatly improves the efficiency of fog harvest. The results show that the chemical gradient and structural gradient actuation we constructed on the melamine sponge surface can effectively improve the fog collection efficiency. A surface with a linear hump-valley mixed wettability pattern is designed, and it is proved that fog collection efficiency can be effectively improved at the droplet capture and transfer stage and transport stage respectively. This study highlights a simple and cheap integrated fog harvester material design.
RESUMO
OBJECTIVES: This study aimed to explore the association between multiple metals' exposure and children's height. METHODS: We collected urine samples and physical measurement data of 1477 preschoolers in China. Children's actual height was measured, and whether reached target height was also assessed. Logistic regression analysis was performed to explore the association between heavy metals and height. The least absolute shrinkage and selection operator regression was used to select the urinary metals, which were highly correlated. RESULTS: In the single-metal model after adjusting for potential confounders, urinary iron, aluminum, nickel, chrome, titanium, vanadium, selenium, rubidium, and thallium levels were negatively associated with actual height. Urinary iron, aluminum, nickel, and chrome concentrations were also negatively associated with target height. CONCLUSIONS: The findings suggested that some urinary metal exposure might be associated with height in preschoolers.
Assuntos
Metais Pesados , Níquel , Criança , Humanos , Alumínio , China/epidemiologia , População do Leste Asiático , Ferro , Metais Pesados/toxicidadeRESUMO
Magnetic resonance imaging (MRI) is a promising non-invasive method to assess cartilage regeneration based on the quantitative relationship between MRI features and concentrations of the major components in the extracellular matrix (ECM). To this end, in vitro experiments are performed to investigate the relationship and reveal the underlying mechanism. A series of collagen (COL) and glycosaminoglycan (GAG) solutions at different concentrations are prepared, and T1 and T2 relaxation times are measured with or without a contrast agent (Gd-DTPA2-) by MRI. Fourier transform infrared spectrometry is also used to measure the contents of biomacromolecule-bound water and other water, allowing theoretical derivation of the relationship between biomacromolecules and the resulting T2 values. It has been revealed that the MRI signal in the biomacromolecule aqueous systems is mainly influenced by the protons in hydrogens of biomacromolecule-bound water, which we divide into inner-bound water and outer-bound water. We have also found that COL results in higher sensitivity of bound water than GAG in T2 mapping. Owing to the charge effect, GAG regulates the penetration of the contrast agent during dialysis and has a more significant effect on T1 values than COL. Considering that COL and GAG are the most abundant biomacromolecules in the cartilage, this study is particularly useful for the real-time MRI-guided assessment of cartilage regeneration. A clinical case is reported as an in vivo demonstration, which is consistent with our in vitro results. The established quantitative relation plays a critical academic role in establishing an international standard ISO/TS24560-1:2022 'Clinical evaluation of regenerative knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping' drafted by us and approved by International Standard Organization.
RESUMO
RATIONALE: Atorvastatin is a commonly used statin for the treatment of hypercholesterolemia in people at high risk for coronary, cerebrovascular, and peripheral artery disease. However, fatal liver failure due to atorvastatin treatment has been rarely reported, especially during the very short incubation period. PATIENT CONCERNS: A 63-year-old male patient was admitted due to unexplained chest pain. After admission, his liver function had decreased < 24 hours after taking 20 mg tablets of atorvastatin due to lacunar infarction, which was improved after drug withdrawal. The treatment regimen was restarted 15 days later, but within 16 hours, the patient developed multiple organ failure, including liver failure and renal failure. DIAGNOSES: The pathological results after 7 days indicated focal inflammatory necrosis, virus and autoimmune correlation tests were negative, which did not rule out drug-induced liver injury. Interventions: receiving artificial liver therapy, continuous renal replacement therapy and other organ support treatment. OUTCOMES: The patient died 18 days after admission. LESSONS: Statin idiosyncratic liver injury is very rare, but the consequences can be serious.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Falência Hepática , Masculino , Humanos , Pessoa de Meia-Idade , Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Falência Hepática/induzido quimicamente , Hipercolesterolemia/tratamento farmacológicoRESUMO
Magnetic hyperthermia therapy (MHT) is a promising new modality to deal with solid tumors, yet the low magnetic-heat conversion efficacy, magnetic resonance imaging (MRI) artifacts, easy leakage of magnetic nanoparticles, and thermal resistance are the main obstacles to expand its clinical applications. Herein, a synergistic strategy based on a novel injectable magnetic and ferroptotic hydrogel is proposed to overcome these bottlenecks and boost the antitumor efficacy of MHT. The injectable hydrogel (AAGel) exhibiting a sol-gel transition upon heating is made of arachidonic acid (AA)-modified amphiphilic copolymers. Ferrimagnetic Zn0.4Fe2.6O4 nanocubes with high-efficiency hysteresis loss mechanism are synthesized and co-loaded into AAGel with RSL3, a potent ferroptotic inducer. This system maintains the temperature-responsive sol-gel transition, and provides the capacity of multiple MHT and achieves accurate heating after a single injection owing to the firm anchoring and uniform dispersion of nanocubes in the gel matrix. The high magnetic-heat conversion efficacy of nanocubes coupled with the application of echo limiting effect avoids the MRI artifacts during MHT. Besides the function of magnetic heating, Zn0.4Fe2.6O4 nanocubes combined with multiple MHT can sustain supply of redox-active iron to generate reactive oxygen species and lipid peroxides and accelerate the release of RLS3 from AAGel, thus enhancing the antitumor efficacy of ferroptosis. In turn, the reinforced ferroptosis can alleviate the MHT-triggered thermal resistance of tumors by impairment of the protective heat shock protein 70. The synergy strategy achieves the complete elimination of CT-26 tumors in mice without causing local tumor recurrence and other severe side effects.
Assuntos
Ferroptose , Hipertermia Induzida , Nanopartículas , Neoplasias , Animais , Camundongos , Hipertermia Induzida/métodos , Hidrogéis , Neoplasias/terapia , Linhagem Celular TumoralRESUMO
The development of dual chemodynamic therapy and NO therapy can significantly improve the efficiency of cancer treatment. Therefore, designing a multifunctional agent to take full advantage of them and maximize their therapeutic effect remains a challenging goal. Herein, we have developed a novel LDHzyme by the confinement of L-arginine (L-Arg) on the surface of Mn-LDH nanosheets. The LDHzyme can exhibit multiple enzyme-like catalytic activities, including peroxidase (POD), oxidase (OXD), and nitric oxide synthase (iNOS). Based on these enzyme-mimicking properties, LDHzyme possesses significant catalytic efficiency with a high maximum velocity of 1.41 × 10-6 M s-1, which is higher than the majority of other nanozymes. In addition, this LDHzyme can exhibit outstanding NO-enhanced lethality of ROS and further improve its efficacy. The therapeutic effect of LDHzyme has been verified to significantly inhibit tumor growth in HeLa xenograft Balb/c nude mice models, as demonstrated in both in vitro and in vivo models, revealing the promising prospects of NO-enhanced multi-enzyme dynamic therapy (MDT). These results open up an opportunity to enable the utilization of an LDH-based nanozyme as a curative nanosystem to inhibit tumor growth.
Assuntos
Neoplasias , Camundongos , Animais , Humanos , Camundongos Nus , Peroxidase , Oxirredutases , CatáliseRESUMO
The olivine phosphate family has been widely utilized as cathode materials for high-performance lithium-ion batteries. However, limited energy density and poor rate performance caused by low electronic and ionic conductivities are the main obstacles that need to be overcome for their widespread application. In this work, atomic simulations have been performed to study the effects of lattice strains on the Li+ ion migration energy barrier in olivine phosphates LiMPO4 (M = Mn, Fe, Co) and (LiFePO4)n(LiMnPO4)m superlattices (SLs). The (LiFePO4)n(LiMnPO4)m superlattices include three ratios of LFP/LMP, namely SL3 + 1, SL1 + 1 and SL1 + 3, each of which is along three typical (100), (010) and (001) orientations. We mainly discuss two migration paths of Li+ ions: the low-energy path A channel parallel to the b-axis and the medium-energy path B channel parallel to the c-axis. It is found that the biaxial tensile strain perpendicular to the migration path is most beneficial to reduce the migration energy barrier of Li+ ions, and the strain on the b-axis has a dominant effect on the energy barrier of Li+ ion migration. For path A, SL3 + 1 alternating periodically along the (010) orientation can obtain the lowest Li ion migration energy barrier. For path B, SL1 + 3 is the most favorable for Li+ ion migration, and there is no significant difference among the three orientations. Our work provides reference values for cathode materials and battery design.
RESUMO
BACKGROUND: Essential hypertension (EH) was associated with mitochondrial tRNA mutations. AIMS: This study was designed to assess the association between EH and mitochondrial dysfunction. METHODS: A total of 30 individuals from two different Chinese families exhibit maternally inherited EH were assessed for genetic, clinical, and biochemical phenotypes pertaining to EH and mitochondrial functionality. These analyses included assessments of tRNALeu(UUR) 3261A > G mutation status, mitochondrial membrane permeability, mitochondria-associated ATP and reactive oxygen species (ROS) generation, and electron transport chain functionality. RESULTS: EH was detected in 6 total analyzed members of the two families assessed in the present study, with its initial age of onset and presentation varying among patients. These patients with EH exhibited the tRNALeu(UUR) 3261A > G mutation and were of the B5 and D4 Eastern Asian mitochondrial haplogroups. This 3261A > G mutation was predicted to result in disruption of normal tRNALeu(UUR) activity owing to the destabilization of conserved base pairing (30A-40U). Consistent with this prediction, we found that cybrid cell lines exhibiting this 3261A > G mutation exhibited a ~49.05% decrease in baseline tRNALeu(UUR) levels. These cells additionally exhibited ~44.81% reductions in rates of mitochondrial translation. CONCLUSIONS: To facilitate future molecular diagnosis, the 3261A > G mutation should be included in the list of hereditary risk factors. Our findings will aid in the counseling of EH families.