RESUMEN
Fluoro-substitution solvents have achieved great success in electrolyte engineering for high-energy lithium metal batteries, which, however, is beset by low solvating power, thermal and chemical instability, and possible battery swelling. Instead, we herein introduce cyanogen as the electron-withdrawing group to enhance the oxidative stability of ether solvents, in which cyanogen and ether oxygen form the chelating structure with Li+ not notably undermining the solvating power. Cyano-group strongly bonds with transition metals (TMs) of NCM811 cathode to attenuate the catalytic reactivity of TMs toward bulk electrolytes. Besides, a stable and uniform cathode-electrolyte interphase (CEI) inhibits the violent oxidation decomposition of electrolytes and guarantees the structural integrity of the NCM811 cathode. Also, a N-containing and LiF-rich solid-electrolyte interphase (SEI) in our electrolyte facilitates fast Li+ migration and dense Li deposition. Accordingly, our electrolyte enables a stable cycle of Li metal anode with Coulombic efficiency of 98.4% within 100 cycles. 81.8% capacity of 4.3 V NCM811 cathode remains after 200 cycles. Anode-free pouch cells with a capacity of 125 mAh maintain 76% capacity after 100 cycles, corresponding to an energy density of 397.5 Wh kg-1.
RESUMEN
Antibiotics are widely used as fungicides because of their antibacterial and bactericidal effects. However, it is necessary to control their dosage. If the amount of antbiotics is too much, it cannot be completely metabolized and absorbed, will pollute the environment, and have a great impact on human health. Many antibiotics usually left in factory or aquaculture wastewater pollute the environment, so it is vital to detect the content of antibiotics in wastewater. This article summarizes several common methods of antibiotic detection and pretreatment steps. The detection methods of antibiotics in wastewater mainly include immunoassay, instrumental analysis method, and sensor. Studies have shown that immunoassay can detect deficient concentrations of antibiotics, but it is affected by external factors leading to errors. The detection speed of the instrumental analysis method is fast, but the repeatability is poor, the price is high, and the operation is complicated. The sensor is a method that is currently increasingly studied, including electrochemical sensors, optical sensors, biosensors, photoelectrochemical sensors, and surface plasmon resonance sensors. It has the advantages of fast detection speed, high accuracy, and strong sensitivity. However, the reproducibility and stability of the sensor are poor. At present, there is no method that can comprehensively integrate the advantages. This paper aims to review the enrichment and detection methods of antibiotics in wastewater from 2020 to the present. It also aims to provide some ideas for future research directions in this field.
Asunto(s)
Antibacterianos , Aguas Residuales , Contaminantes Químicos del Agua , Aguas Residuales/análisis , Aguas Residuales/química , Antibacterianos/análisis , Contaminantes Químicos del Agua/análisis , Técnicas Biosensibles/métodos , Inmunoensayo/métodosRESUMEN
Objective To understand the differences in the demand,preference,and tendency for elderly care services between urban and rural areas in the Pearl River Delta (PRD),and to provide reference for the planning and balanced allocation of elderly care resources in urban and rural areas. Methods Using the multi-stage stratified random sampling method,we selected 7 community health service centers in 2 prefecture-level cities in the PRD and conducted a questionnaire survey on the elderly care service demand,preference,and tendency among 1919 regular residents aged 60 years and above who attended the centers. Results A total of 641 urban elderly residents (33.4%) and 1278 rural elderly residents (66.6%) were surveyed in the PRD.The urban and rural elderly residents showed differences in the child number (χ2=43.379,P<0.001),willingness to purchase socialized elderly care services (χ2=104.141,P<0.001),and attitudes to the concept of raising child to avoid elderly hardship (χ2=65.632,P<0.001).The proportion (71.8%) of rural elderly residents who prefer family-based elderly care was higher than that (57.1%) of urban elderly residents (χ2=41.373,P<0.001).The proportion (62.2%) of urban elderly residents clearly expressing their willingness to choose institutions for elderly care was higher than that (44.0%) of rural elderly residents (χ2=57.007,P<0.001).Compared with family-based elderly care,the willingness to choose institutional or community-based in-house elderly care was low among the urban elderly residents with surplus monthly household income or balanced income and expenditure;urban males,those with college education background or above,and those who purchased socialized elderly care services tended to prefer community-based in-house elderly care.In rural areas,the elderly residents who had local household registry were prone to choose institutional or community-based in-house elderly care,while those who had more than one child and those who were satisfied with the current living conditions were less willing to choose community-based in-house elderly care. Conclusions It is suggested that the urban-rural differences in the elderly care service demand,preference and tendency should be fully considered in the planning and allocation of urban and rural elderly care resources.Efforts remain to be made to develop diversified social elderly care services tailored to the characteristics of urban and rural areas.
Asunto(s)
Población Rural , Población Urbana , Humanos , Anciano , China , Masculino , Femenino , Persona de Mediana Edad , Encuestas y Cuestionarios , Servicios de Salud para Ancianos/estadística & datos numéricos , Anciano de 80 o más Años , Necesidades y Demandas de Servicios de SaludRESUMEN
Yttrium aluminum garnet (YAG) crystals are an important gain medium in thin-sheet solid-state lasers, and their processing quality directly affects the performance of solid-state lasers. But it is difficult to achieve high efficiency and high quality of YAG crystals by traditional chemical mechanical polishing (CMP). In this study, we developed a new polishing slurry for photoassisted chemical mechanical polishing (PCMP) of YAG crystals. The polishing slurry is composed of peroxymonosulfate (PMS), manganese ferrite (MnFe2O4), alumina (Al2O3) abrasives, and deionized water. PCMP is conducted in an ultraviolet (UV) light environment. When employing this polishing slurry for PCMP processing of YAG crystals, the material removal rate (MRR) achieved 250 nm/min and the surface roughness achieved 0.35 nm Sa. The experiments verified that both UV light and MnFe2O4 can effectively activate PMS to produce active free radicals and further enhance the chemical action of the polishing slurry. X-ray photoelectron spectroscopy (XPS) analysis results indicated that active radicals reacted with the surface structure of the crystal and removed the aluminum-oxygen octahedron in large quantities from it. The structural defects reduced the surface hardness of the crystal, which means that active free radicals can modify the crystal surface materials.
RESUMEN
Objective To compare the functional status of diabetic patients with and without nephropathy and identify the items that diabetic patients with nephropathy are more likely to develop dysfunction than diabetic patients without nephropathy based on the international classification of functioning,disability and health rehabilitation set(ICF-RS).Methods A cross-sectional study was conducted.A total of 320 diabetic patients hospitalized in Guangdong Provincial Hospital of Chinese Medicine from August 2021 to February 2022 were selected and assigned into a group with nephropathy and a group without nephropathy.The general characteristics,clinical examination,and laboratory findings were compared by the t test,rank sum test,and Chi-squared test.The functional status of the patients was compared between the two groups by the t test based on the ICF-RS.Logistic regression was employed to control interferential factors between the two groups and identify the association between nephropathy and ICF-RS problematic items among diabetic patients.Results The diabetic patients with nephropathy had more problematic items in ICF-RS(P<0.001),the body function dimension(P=0.003),the activity dimension(P<0.001),and the participation dimension(P<0.001)than those without nephropathy.Moreover,the diabetic patients with nephropathy experienced severer problems in 5 body function items(energy and drive functions,sleep functions,sexual functions,exercise tolerance functions,and muscle power functions),10 activity items(transferring oneself,walking,moving around using equipment,moving around,washing oneself,caring for body parts,toileting,dressing,doing housework,and looking after one's health),and 4 participation items(using transportation,assisting others,basic interpersonal interactions,and recreation and leisure)(all P<0.05).The Logistic regression results showed that compared with the diabetic patients without nephropathy,the diabetic patients with nephropathy were more likely to develop problems in energy and drive functions(aOR=4.35,95%CI=1.28-14.79,P=0.019),emotional functions(aOR=1.88,95%CI=1.06-3.34,P=0.031),sexual functions(aOR=3.39,95%CI=1.82-6.34,P<0.001),moving around(aOR=3.11,95%CI=1.76-5.52,P<0.001),doing housework(aOR=17.48,95%CI=3.57-85.60,P<0.001),looking after one's health(aOR=1.97,95%CI=1.13-3.43,P=0.017),using transportation(aOR=2.59,95%CI=1.38-4.88,P=0.003),and recreation and leisure(aOR=2.52,95%CI=1.46-4.35,P<0.001).Conclusion Compared with the diabetic patients without nephropathy,the patients with nephropathy suffer more ICF-RS problematic items and are more likely to develop dysfunction in certain items in all the three dimensions.
Asunto(s)
Diabetes Mellitus , Personas con Discapacidad , Enfermedades Renales , Humanos , Evaluación de la Discapacidad , Estudios Transversales , Estado Funcional , Personas con Discapacidad/rehabilitación , Actividades CotidianasRESUMEN
A concise and divergent synthesis of the polychlorinated marine steroids clionastatin A and B from inexpensive testosterone has been achieved through a unique two-stage chlorination-oxidation strategy. Key features of the two-stage synthesis include (1) conformationally controlled, highly stereoselective dichlorination at C1 and C2 and C4-OH-directed C19 oxygenation followed by a challenging neopentyl chlorination to install three chlorine atoms; (2) desaturation through one-pot photochemical dibromination-reductive debromination and anti-Markovnikov olefin oxidation by photoredox-metal dual catalysis to enhance the oxidation level of the backbone; and (3) Wharton transposition to furnish the D-ring enone. This synthesis proved that the introduction of the C19 chloride in the early stage of the synthesis secured the stability of the backbone against susceptibility to aromatization during the oxidation stage.
Asunto(s)
Alquenos , Cloro , Catálisis , Oxidación-Reducción , EstereoisomerismoRESUMEN
The electrochemical performance of rechargeable Mg batteries (RMBs) is primarily determined by the cathodes. However, the strong interaction between highly polarized Mg2+ and the host lattice is a big challenge for inorganic cathode materials. While endowed with weak interaction with Mg2+ , organic polymers are capable of fast reaction kinetics. Besides, with the advantages of light weight, abundance, low cost, and recyclability, polymers are deemed as ideal cathode materials for RMBs. Although polymer cathodes have remarkably progressed in recent years, there are still significant challenges to overcome before reaching practical application. In this perspective, the challenges faced by polymer cathodes are critically focused, followed by the retrospection of efforts devoted to design polymers. Some feasible strategies are proposed to explore new structures and chemistries for the practical application of polymer cathodes in RMBs.
RESUMEN
Predicting the photophoretic force exerted on an optical absorptive particle in a gaseous medium is a challenging problem because the problems of electromagnetic scattering, heat transfer, and gaseous molecule dynamics are involved and coupled with each other. Based on the calculation of the source function distribution inside a homogeneous sphere excited by a Bessel beam using the generalized Lorenz-Mie theory, analytical expressions of the asymmetry vector, which is the key quantity in the calculation of photophoretic force, are given using the adjoint boundary value method. Numerical simulations are performed to analyze the influences of polarization, the half-cone angle, and the beam order of the incident beam, particle size, and absorptivity of the particle on the asymmetry vector for both on-axis and off-axis illuminations. Longitudinal and transverse photophoretic forces on a homogeneous sphere are displayed for the slip-flow regime of gaseous media. The results offer important insights into the working mechanism underpinning the development of heat-mediated optical manipulation techniques and the measurement of the refractive index of particles.
RESUMEN
The outbreak of coronavirus disease (COVID-19) has been a nightmare to citizens, hospitals, healthcare practitioners, and the economy in 2020. The overwhelming number of confirmed cases and suspected cases put forward an unprecedented challenge to the hospital's capacity of management and medical resource distribution. To reduce the possibility of cross-infection and attend a patient according to his severity level, expertly diagnosis and sophisticated medical examinations are often required but hard to fulfil during a pandemic. To facilitate the assessment of a patient's severity, this paper proposes a multi-modality feature learning and fusion model for end-to-end covid patient severity prediction using the blood test supported electronic medical record (EMR) and chest computerized tomography (CT) scan images. To evaluate a patient's severity by the co-occurrence of salient clinical features, the High-order Factorization Network (HoFN) is proposed to learn the impact of a set of clinical features without tedious feature engineering. On the other hand, an attention-based deep convolutional neural network (CNN) using pre-trained parameters are used to process the lung CT images. Finally, to achieve cohesion of cross-modality representation, we design a loss function to shift deep features of both-modality into the same feature space which improves the model's performance and robustness when one modality is absent. Experimental results demonstrate that the proposed multi-modality feature learning and fusion model achieves high performance in an authentic scenario.
RESUMEN
Earth-abundant Fe2O3 is a promising material for the negative electrode of supercapacitors by virtue of its wide potential windows. However, the unsatisfactory electrical conductivity and poor ionic diffusion rate within Fe2O3 results in degraded electrochemical performance. In this work, to address these issues, we demonstrate an easy method to synthesize Fe-based zeolitic imidazolate framework (Fe-ZIF) derived α-Fe2O3@C with remarkable supercapacitive properties. The as-obtained α-Fe2O3@C electrode, with the particular benefit of dispersed distribution of carbon, enabling fast electrochemical response, presents a prospective specific capacitance of 161 Fg-1 at a current density of 1 Ag-1. Furthermore, by using the α-Fe2O3@C architecture as the negative electrode, we fabricated a supercapacitor with Na0.5MnO2 as the positive electrode. Our supercapacitor shows a high energy density of 25 Whkg-1, while the corresponding power density is 2400 Wkg-1 at a current density of 2 Ag-1.
RESUMEN
Clarifying the interaction between active materials and current collectors of the same electrode is crucial for understanding the electrochemical energy storage mechanism and designing high-performance supercapacitors. The interaction mechanism is mainly due to the evolution of chemical bonding. Here, we explore the chemical bonding evolution between cobalt-nickel layered double hydroxide and carbon fiber paper by using ex situ x-ray photoelectron spectroscopy during redox reaction. The results reveal that chemical bonding corresponds to more ionic states at the lowest potential and more covalent states at the highest potential. Attributed to the formation of C-O-Metal (Co, Ni) chemical bonds, high capacitance with enhanced stability and rate capability is obtained. The Co-Ni layered double hydroxide electrode exhibits a high areal and mass specific capacitance of 0.55 and 952 F g-1 at a low mass loading of 0.58 mg cm-2. At a high mass loading of 3.59 mg cm-2, high areal and mass specific capacitance of 3.24 F cm-2 and 811 F g-1 are obtained. Based on this, a hybrid supercapacitor is fabricated with high-mass-loading Co-Ni layered double hydroxide and active carbon as positive and negative electrodes, respectively. As a result, this device delivers a prominent energy density of 20.9 Wh cm-3 at a power density of 0.12 W cm-3.
RESUMEN
We sought to investigate the role of the adenosine A1 receptors (A1ARs) in white matter lesions under chronic cerebral hypoperfusion (CCH) and explore the potential repair mechanisms by activation of the receptors. A right unilateral common carotid artery occlusion (rUCCAO) method was used to construct a CCH model. 2-chloro-N6-cyclopentyladenosine (CCPA), a specific agonist of A1ARs, was used to explore the biological mechanisms of repair in white matter lesions under CCH. The expression of mammalian target of rapamycin (mTOR), phosphorylation of mTOR (P-mTOR), myelin basic protein (MBP, a marker of white matter myelination) were detected by Western-blot. Pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokine interleukin-10 (IL-10) levels were determined by ELISA. Compared with the control groups on week 2, 4 and 6, in CCPA-treated groups, the ratio of P-mTOR/mTOR, expression of MBP and IL-10 increased markedly, while the expression of TNF-α reduced at week 6. In conclusion, A1ARs appears to reduce inflammation in white matter via the mTOR signaling pathway in the rUCCAO mice. Therefore, A1ARs may serve as a therapeutic target during the repair of white matter lesions under CCH.
Asunto(s)
Encéfalo/irrigación sanguínea , Leucoencefalopatías/patología , Receptor de Adenosina A1/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Encéfalo/metabolismo , Arteria Carótida Común/patología , Estenosis Carotídea/complicaciones , Inflamación/metabolismo , Interleucina-10/metabolismo , Leucoencefalopatías/etiología , Leucoencefalopatías/metabolismo , Ligadura , Masculino , Ratones Endogámicos C57BL , Proteína Básica de Mielina/metabolismo , Fosforilación , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: The objective of the present study was to clarify the relationship between the neuroprotective effects of curcumin and the classical wnt signaling pathway. METHOD: Using Sprague-Dawley rats at a gestational age of 14.5 d, we isolated neural stem cells from the anterior two-thirds of the fetal rat brain. The neural stem cells were passaged three times using the half media replacement method and identified using cellular immunofluorescence. After passaging for three generations, we cultured cells in media without basic fibroblast growth factor and epidermal growth factor. Then we treated cells in five different ways, including a blank control group, a group treated with IWR1 (10 µmol/L), a group treated with curcumin (500 nmol/L), a group treated with IWR1 + curcumin, and a group treated with dimethyl sulfoxide (10 µmol/L). We then measured the protein and RNA expression levels for wnt3a and ß-catenin using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Western-blotting: after the third generation of cells had been treated for 72 h, we observed that wnt3a and ß-catenin expression was significantly increased in the group receiving 500 nmol/L curcumin but not in the other groups. Furthermore, cells in the IWR1-treated group showed decreased wnt3a and ß-catenin expression, and wnt3a and ß-catenin was also decreased in the IWR1 + 500 nmol/L curcumin group. No obvious change was observed in the dimethyl sulfoxide group. RT-PCR: RT-PCR showed similar changes to those observed with the Western blotting experiments. CONCLUSIONS: Our study suggests that curcumin can activate the wnt signaling pathway, which provides evidence that curcumin exhibits a neuroprotective effect through the classical wnt signaling pathway.
Asunto(s)
Curcumina/farmacología , Células-Madre Neurales/citología , Células-Madre Neurales/efectos de los fármacos , Neuronas/citología , Fármacos Neuroprotectores/farmacología , Vía de Señalización Wnt/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/farmacología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Células Cultivadas , Femenino , Embarazo , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Vía de Señalización Wnt/fisiología , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Flexibility endows humidity sensors with new applications in human health monitoring except for traditionally known environmental humidity detection in recent years. In this study, a flexible, mesh-structured, and self-supported humidity sensor was designed and manufactured by direct writing in a homemade two-dimensional stepping numerical control workstation. Bacterial cellulose with humidity sensitivity and good film-forming properties was applied as the self-supporting substrate, in which conductive activated carbon and water-absorptive magnesium chloride (MgCl2) were incorporated. The humidity sensing performance of the printed sensor was measured and optimized. Besides, the fundamental insight into the sensing mechanism of the printed humidity sensor was analyzed by a complex impedance spectrum. The multifunctional applications of the self-supported humidity sensor were demonstrated by human breathing detection, noncontact distance sensing, and speaking recognition. The simple self-supported structure combined with the meshed attribute of the flexible sensor showed large use potential in real-time monitoring of human respiration, voice detection, environmental humidity monitoring, and noncontact switches.
RESUMEN
To establish the sound quality evaluation model of roller chain transmission system, we collect the running noise under different working conditions. After the noise samples are preprocessed, a group of experienced testers are organized to evaluate them subjectively. Mel frequency cepstral coefficient (MFCC) of each noise sample is calculated, and the MFCC feature map is used as an objective evaluation. Combining with the subjective and objective evaluation results of the roller chain system noise, we can get the original dataset of its sound quality research. However, the number of high-quality noise samples is relatively small. Based on the sound quality research of various chain transmission systems, a novel method called multi-source transfer learning convolutional neural network (MSTL-CNN) is proposed. By transferring knowledge from multiple source tasks to target task, the difficulty of small sample sound quality prediction is solved. Compared with the problem that single source task transfer learning has too much error on some samples, MSTL-CNN can give full play to the advantages of all transfer learning models. The results also show that the MSTL-CNN proposed in this paper is significantly better than the traditional sound quality evaluation methods.
RESUMEN
Currently, immune checkpoint blockade (ICB) therapies that target the programmed cell death ligand-1 (PD-L1) have been used as revolutionary cancer treatments in the clinic. Apart from restoring the antitumor response of cytotoxic T cells by blocking the interaction between PD-L1 on tumor cells and programmed cell death-1 (PD-1) on T cells, PD-L1 proteins were also newly revealed to possess the capacity to accelerate DNA damage repair (DDR) and enhance tumor growth through multiple mechanisms, leading to the impaired efficacy of tumor therapies. Nevertheless, current free anti-PD-1/PD-L1 therapy still suffered from poor therapeutic outcomes in most solid tumors due to the non-selective tumor accumulation, ineludible severe cytotoxic effects, as well as the common occurrence of immune resistance. Recently, nanoparticles with efficient tumor-targeting capacity, tumor-responsive prosperity, and versatility for combination therapy were identified as new avenues for PD-L1 targeting cancer immunotherapies. In this review, we first summarized the multiple functions of PD-L1 protein in promoting tumor growth, accelerating DDR, as well as depressing immunotherapy efficacy. Following this, the effects and mechanisms of current clinically widespread tumor therapies on tumor PD-L1 expression were discussed. Then, we reviewed the recent advances in nanoparticles for anti-PD-L1 therapy via using PD-L1 antibodies, small interfering RNA (siRNA), microRNA (miRNA), clustered, regularly interspaced, short palindromic repeats (CRISPR), peptide, and small molecular drugs. At last, we discussed the challenges and perspectives to promote the clinical application of nanoparticles-based PD-L1-targeting therapy.
Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Inmunoterapia , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Terapia Combinada , Microambiente TumoralRESUMEN
This paper proposes a hybrid radiance field representation for unbounded immersive light field reconstruction which supports high-quality rendering and aggressive view extrapolation. The key idea is to first formally separate the foreground and the background and then adaptively balance learning of them during the training process. To fulfill this goal, we represent the foreground and background as two separate radiance fields with two different spatial mapping strategies. We further propose an adaptive sampling strategy and a segmentation regularizer for more clear segmentation and robust convergence. Finally, we contribute a novel immersive light field dataset, named THUImmersive, with the potential to achieve much larger space 6DoF immersive rendering effects compared with existing datasets, by capturing multiple neighboring viewpoints for the same scene, to stimulate the research and AR/VR applications in the immersive light field domain. Extensive experiments demonstrate the strong performance of our method for unbounded immersive light field reconstruction.
RESUMEN
Currently, limited photosensitizers possess the capacity to reverse tumor hypoxia and reduce programmed death ligand-1 (PD-L1) and transforming growth factor-ß (TGF-ß) expression simultaneously, hindering the perfect photodynamic therapy (PDT) effect due to acquired immune resistance and the tumor hypoxic microenvironment. To tackle these challenges, in this research, we demonstrated that mitochondrial energy metabolism depression can be utilized as an innovative and efficient approach for reducing the expression of PD-L1 and TGF-ß simultaneously, which may offer a design strategy for a more ideal PDT nanosystem. Through proteomic analysis of 5637 cells, we revealed that tamoxifen (TMX) can incredibly regulate PD-L1 expression in tumor cells. Then, to selectively deliver clinically used mitochondrial energy metabolism depressant TMX to solid tumors as well as design an ideal PDT nanosystem, we synthesized MHI-TMX@ALB by combining a mitochondria-targeted heptamethine cyanine PDT-dye MHI with TMX through self-assembly with albumin (ALB). Interestingly enough, the MHI-TMX@ALB nanoparticle demonstrated effective reversion of tumor hypoxia and inhibition of PD-L1 protein expression at a lower dosage (7.5 times to TMX), which then enhanced the efficacy of photodynamic immunotherapy via enhancing T-cell infiltration. Apart from this, by leveraging the heptamethine dye's targeting capacity toward tumors and TMX's role in suppressing TGF-ß, MHI-TMX@ALB also more effectively mitigated 4T1 tumor lung metastasis development. All in all, the MHI-TMX@ALB nanoparticle could be used as a multifunctional economical PD-L1 and TGF-ß codepression immune-regulating strategy, broadening the potential clinical applications for a more ideal PDT nanosystem.
Asunto(s)
Antígeno B7-H1 , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Factor de Crecimiento Transformador beta , Ligandos , Proteómica , Inmunoterapia , Mitocondrias/metabolismo , Factores de Crecimiento Transformadores , Microambiente Tumoral , Línea Celular TumoralRESUMEN
Currently, the typical combination therapy of programmed death ligand-1 (PD-L1) antibodies with radiotherapy (RT) still exhibits impaired immunogenic antitumor response in clinical due to lessened DNA damage and acquired immune tolerance via the upregulation of some other immune checkpoint inhibitors. Apart from this, such combination therapy may raise the occurrence rate of radiation-induced lung fibrosis (RIPF) due to enhanced systemic inflammation, leading to the ultimate death of cancer patients (average survival time of about 3 years). Therefore, it is newly revealed that mitochondria energy metabolism regulation can be used as a novel effective PD-L1 and transforming growth factor-ß (TGF-ß) dual-downregulation method. Following this, IR-TAM is prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68 with oxidative phosphorylation (OXPHOS) inhibitor Tamoxifen (TAM), which then self-assembled with albumin (Alb) to form IR-TAM@Alb nanoparticles. By doing this, tumor-targeting IR-TAM@Alb nanoparticle effectively reversed tumor hypoxia and depressed PD-L1 and TGF-ß expression to sensitize RT. Meanwhile, due to the capacity of heptamethine cyanine dye in targeting RIPF and the function of TAM in depressing TGF-ß, IR-TAM@Alb also ameliorated fibrosis development induced by RT.
Asunto(s)
Metabolismo Energético , Mitocondrias , Fibrosis Pulmonar , Animales , Ratones , Fibrosis Pulmonar/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Modelos Animales de Enfermedad , Factor de Crecimiento Transformador beta/metabolismo , Humanos , Radioterapia/métodos , Radioterapia/efectos adversos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genéticaRESUMEN
BACKGROUND: There are currently many imaging indicators for idiopathic normal pressure hydrocephalus (iNPH). However, their diagnostic performance has not been well compared, especially in differentiating iNPH from Alzheimer's disease (AD). This study aimed to evaluate the diagnostic performance of these imaging indicators in differentiating iNPH from AD. METHODS: We retrospectively collected patients with iNPH from the West China Hospital between June 2016 and December 2023. Age-sex-matched patients with AD and healthy controls (HCs) are included as controls (ChiCTR2300070078, March 2023). Twelve imaging indicators were evaluated on MRI, including disproportionately enlarged subarachnoid space hydrocephalus (DESH), Evans' index (EI), callosal angle, z-EI, temporal horn, dilated Sylvian fissure, focal sulcal dilation, tight high convexity, deep white matter hyperintensities, periventricular hyperintensities, DESH scale, and Simplified Radscale. We analyzed the receiver operating characteristic curves and calculated the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. RESULTS: A total of 46 patients with iNPH (mean age: 73.1 ± 6.5; 35 males), 46 patients with AD (mean age: 73.0 ± 6.6; 35 males), and 46 HCs (mean age: 73.0 ± 5.9; 35 males) were included. The largest area under the receiver operating characteristic curve (AUC) was found in EI (0.93; 95â¯% CI: 0.89-0.98) and z-EI (0.93; 95â¯% CI: 0.87-0.98). DESH scale ≥ 6 had the highest specificity (93â¯%, 43/46). CONCLUSION: EI and z-EI had the best diagnostic performance in differentiating iNPH from AD. The DESH scale could assist in diagnosing iNPH due to its high specificity.