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BACKGROUND: Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. METHODS: In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP-RIPK1-NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1ß and in the post-traumatic OA model. RESULTS: In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. CONCLUSIONS: These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis.
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FN-kappa B , Osteoartritis , Humanos , Ratas , Animales , FN-kappa B/metabolismo , Osteoartritis/terapia , Osteoartritis/patología , Ondas Ultrasónicas , Inflamación/patología , Autofagia , Condrocitos , Interleucina-1beta/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Specific peptide-protein interactions play an important role in biosensing systems based on functional peptides; however, the non-specific interactions with unrelated biomolecules and poor proteolytic stability restrict the clinical application of natural peptides. Here, we leveraged a self-designed multifunctional isopeptide (MISP) to construct an electrochemical biosensing platform for annexin A1 (ANXA1) detection in human blood. The MISP was designed to contain two parts: an antifouling cyclotide cyclo-C(EK)4 and a d-amino acid-containing carbohydrate-mimetic recognizing peptide IF-7 (D-IF7) connected by the isopeptide bond. We have discussed the properties of the cyclotide and illustrated its unique advantage over the natural linear antifouling peptides by molecular dynamics simulations, and the results were further confirmed by dissipative quartz crystal microbalance (QCM-D). In addition, through electrochemical experiments and fluorescence imaging experiments, we demonstrated that the MISP-based biosensor possessed excellent antifouling ability and proteinase hydrolysis stability. Interestingly, the assaying results of the MISP-biosensor were consistent with those of the commercial ANXA1 kits in a variety of healthy and ANXA1-upregulated clinical blood samples, and, more importantly, for the analysis of blood samples with lower ANXA1 expressions, the sensing capability of the biosensor was greatly superior to that of the kits because of the lower detection limit of the MISP-biosensor. This biosensing platform based on the designed MISP offers enormous potential for achieving accurate biomarker detection with robust operation in complex biological samples.
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Anexina A1 , Técnicas Biosensibles , Ciclotidas , Humanos , Anexina A1/metabolismo , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodosRESUMEN
Cognitive decline is one of the most distinct signs of aging, and age-related cognitive decline is a heterogeneous issue varying in different cognitive domains and has significant differences among older adults. Identifying characteristics of cognitive aging is the basis of cognitive disease for early-detection and healthy aging promotion. In the current chapter, age-related decline of main cognitive domains, including sensory perception, memory, attention, executive function, language, reasoning, and space navigation ability are introduced respectively. From these aspects of cognition, we focus on the age-related effects, age-related cognitive diseases, and possible mechanisms of cognitive aging.
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Disfunción Cognitiva , Función Ejecutiva , Humanos , Anciano , Envejecimiento/psicología , Cognición , Disfunción Cognitiva/diagnóstico , AtenciónRESUMEN
High performance and cost-effective solar absorbers are crucial for various optical applications, such as solar collection and thermophotovoltaic devices. This study designs and experimentally demonstrates a wide-angle and broadband solar absorber. The proposed absorber is composed of tapered polyimide substrate and Al-Cr-SiO2-Cr-SiO2 thin-film based on the optical interference of the multilayer thin film and excited magnetic resonance of light-trapping structures. The composite process of the colloidal lithography method and magnetron sputtering is employed for efficient fabrication in a large area. The average absorbance is more than 93% from 300 nm to 2500 nm and shows an angular tolerance of up to 60°. The high efficiency and large-area fabrication capability demonstrated by the proposed solar absorber presents future application potential in flexible solar collection devices.
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Biobutanol produced in acetone-butanol-ethanol (ABE) fermentation at batch mode cannot compete with chemically derived butanol because of the low reactor productivity. Continuous fermentation can dramatically enhance productivity and lower capital and operating costs, but are rarely used in industrial fermentation because of increased risks of culture degeneration, cell washout, and contamination. In this study, cells of the asporogenous Clostridium acetobutylicum ATCC55025 were immobilized in a single-pass fibrous-bed bioreactor (FBB) for continuous production of butanol from glucose and butyrate at various dilution rates. Butyric acid in the feed medium helped maintaining cells in the solventogenic phase for stable continuous butanol production. At a dilution rate of 1.88 h-1 , butanol was produced at 9.55 g/L, with a yield of 0.24 g/g and productivity of 16.8 g/L/h, which was the highest productivity ever achieved for biobutanol fermentation and an 80-fold improvement over the conventional ABE fermentation. The extremely high productivity was attributed to the high density of viable cells (~100 g/L at >70% viability) immobilized in the fibrous matrix, which also enabled the cells to better tolerate butanol and butyric acid. The FBB was stable for continuous operation for an extended period of over 1 month.
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Clostridium acetobutylicum , Butanoles , 1-Butanol , Ácido Butírico , Glucosa , Reactores Biológicos , Acetona , FermentaciónRESUMEN
Cellulosic n-butanol from renewable lignocellulosic biomass has gained increased interest. Previously, we have engineered Clostridium cellulovorans, a cellulolytic acidogen, to overexpress the bifunctional butyraldehyde/butanol dehydrogenase gene adhE2 from C. acetobutylicum for n-butanol production from crystalline cellulose. However, butanol production by this engineered strain had a relatively low yield of approximately 0.22 g/g cellulose due to the coproduction of ethanol and acids. We hypothesized that strengthening the carbon flux through the central butyryl-CoA biosynthesis pathway and increasing intracellular NADH availability in C. cellulovorans adhE2 would enhance n-butanol production. In this study, thiolase (thlACA ) from C. acetobutylicum and 3-hydroxybutyryl-CoA dehydrogenase (hbdCT ) from C. tyrobutyricum were overexpressed in C. cellulovorans adhE2 to increase the flux from acetyl-CoA to butyryl-CoA. In addition, ferredoxin-NAD(P)+ oxidoreductase (fnr), which can regenerate the intracellular NAD(P)H and thus increase butanol biosynthesis, was also overexpressed. Metabolic flux analyses showed that mutants overexpressing these genes had a significantly increased carbon flux toward butyryl-CoA, which resulted in increased production of butyrate and butanol. The addition of methyl viologen as an electron carrier in batch fermentation further directed more carbon flux towards n-butanol biosynthesis due to increased reducing equivalent or NADH. The engineered strain C. cellulovorans adhE2-fnrCA -thlACA -hbdCT produced n-butanol from cellulose at a 50% higher yield (0.34 g/g), the highest ever obtained in batch fermentation by any known bacterial strain. The engineered C. cellulovorans is thus a promising host for n-butanol production from cellulosic biomass in consolidated bioprocessing.
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1-Butanol/metabolismo , Celulosa/metabolismo , Clostridium cellulovorans , Ingeniería Metabólica , Microorganismos Modificados Genéticamente , Clostridium cellulovorans/genética , Clostridium cellulovorans/metabolismo , Microorganismos Modificados Genéticamente/genética , Microorganismos Modificados Genéticamente/metabolismoRESUMEN
Pauli spin blockade (PSB) is a significant physical effect in double quantum dot (DQD) systems. In this paper, we start from the fundamental quantum model of the DQD with the electron-electron interaction being considered and then systematically study the PSB effect in DQD by using a recently developed nonperturbative method, the hierarchical equations of motion approach. By checking the current-voltage and nonequilibrium spectral function features, the physical picture of the PSB is explicitly elucidated. Then, various kinds of manipulation of PSBs are discussed, including gate voltage, exchange interaction, and electron spin resonance. Three main characteristics beyond low-order perturbation theory are demonstrated in detail as follows: (1) the finite leakage current in the strongly correlated limit; (2) the enhancement and lifting of PSB by exchange interaction; and (3) the ON-and-OFF switch of PSB by real-time modulation.
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In this study an impedance aptasensor was designed for sensitive, selective, and fast detection of tetracycline (TET) based on an interdigital array microelectrode (IDAM). The IDAM was integrated with impedance detection to miniaturize the conventional electrodes, enhance the sensitivity, shorten the detection time, and minimize interfering effects of non-target analytes in the solution. Due to their excellent conductivity, good biocompatibility, the multi-walled carbon nanotubes (MWCNTs) were used to modify the IDAM to immobilize TET aptamer effectively. The proposed aptasensor produced a sensitive impedance change which was characterized by the electrochemical impedance spectroscopy (EIS). With the addition of TET, the formation of TET-aptamer complex on the surface of MWCNTs modified electrode resulted in an increase of electron transfer resistance (R et). The change of R et depends on the concentration of TET, which is applied for the quantification of TET. A wide linear range was obtained from 10-9 to 10-3 M. The linear regression equation was y(ΔR) = 21.310 × x(LogC) (M) + 217.25. It was successfully applied to detect TET in real milk samples.
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Espectroscopía Dieléctrica/métodos , Nanotubos de Carbono/química , Tetraciclina/análisis , Espectroscopía Dieléctrica/instrumentación , MicroelectrodosRESUMEN
Insects evolve resistance which constrains the sustainable use of insecticides. Spinosyns, a class of environmentally-friendly macrolide insecticides, is not an exception. The mode of inheritance and the mechanisms of resistance to spinosad (the most common spinosyn insecticide) in Frankliniella occidentalis (Western flower thrips, WFT) were investigated in this study. Resistance (170,000-fold) was autosomal and completely recessive. Recent studies showed that deletion of the nicotinic acetylcholine receptor α6 subunit gene resulted in strains of Drosophila melanogaster, Plutella xylostella and Bactrocera dorsalis that are resistant to spinosad, indicating that nAChRα6 subunit maybe important for the toxic action of this insecticide. Conversely, a G275E mutation of this subunit in F. occidentalis was recently proposed as the mechanism of resistance to spinosad. We cloned and characterized nAChRα6 from three susceptible and two spinosad resistant strains from China and the USA. The Foα6 cDNA is 1873bp and the open reading frame is 1458bp which encodes 485 amino acid residues with a predicted molecular weight of 53.5-kDa, the 5' and 3' UTRs are 121 and 294bp, respectively. There was no difference in the cDNA sequence between the resistant and susceptible thrips, suggesting the G275E mutation does not confer resistance in these populations. Ten isoforms of Foα6, arising from alternative splicing, were isolated and did not differ between the spinosad-susceptible and resistant strains. Quantitative real time PCR analysis showed Foα6 was highly expressed in the first instar larva, pupa and adult, and the expression levels were 3.67, 2.47, 1.38 times that of the second instar larva. The expression level was not significantly different between the susceptible and resistant strains. These results indicate that Foα6 is not involved in resistance to spinosad in F. occidentalis from China and the USA.
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Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas , Insecticidas/farmacología , Macrólidos/farmacología , Receptores Nicotínicos/metabolismo , Thysanoptera/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Combinación de Medicamentos , Femenino , Proteínas de Insectos/genética , Masculino , Datos de Secuencia Molecular , Receptores Nicotínicos/genética , Thysanoptera/genética , Thysanoptera/metabolismoRESUMEN
The western flower thrips, Frankliniella occidentalis (Pergande), and the sweetpotato whitefly, Bemisia tabaci (Gennadius), are both invasive insect pests and are present in most of the same agricultural crops without a clear dominance of either species. Here, intra- and interspecific competition in B. tabaci and F. occidentalis was determined under controlled experiments. The results showed that intraspecific competition was distinct in F. occidentalis and that the co-occurrence of B. tabaci had a strong effect on F. occidentalis, resulting in a decrease in oviposition. Significant intraspecific competition was found in B. tabaci, and the coexistence of F. occidentalis had limited effect on the oviposition of B. tabaci. In a selective host plant preference experiment, both F. occidentalis and B. tabaci preferred eggplants most, followed by cucumbers and tomatoes. On cucumber plants, B. tabaci was predominant, whereas on eggplant and tomato plants, F. occidentalis and B. tabaci exhibited comparative competitive abilities during the initial stage. However, over time, higher numbers of B. tabaci than that of F. occidentalis were found on the two host plants. Our in vitro and potted plant experiments indicate that B. tabaci is competitively superior to F. occidentalis, which might help to explain their differential distribution patterns in China.
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Hemípteros/fisiología , Thysanoptera/fisiología , Animales , Conducta Competitiva , Conducta Alimentaria , Femenino , Fertilidad , Cadena Alimentaria , Masculino , Oviposición , Densidad de Población , Especificidad de la EspecieRESUMEN
Live fish transportation is crucial for managing aquaculture but can pose health risks to fish due to stressors encountered during transportation. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a crucial role in the central nervous system and is considered to exhibit anti-stress effects. This study aims to investigate the effects of GABA on the transport water quality, plasma biochemical indices, energy metabolism, and antioxidant capacity of tawny puffer (Takifugu flavidus) under transport stress. Tawny puffer were pretreated by immersing in aquariums containing GABA (final concentrations at 0, 5, 50, and 150 mg/L) seawater for 3 days; then, simulated transport was conducted using oxygen-filled polyethylene bags containing the same concentration of GABA seawater as the pretreatment period. Water samples, plasma, and liver were collected after 0, 6, and 12 h of transport. The results revealed that with the prolongation of transportation time, the control group's water quality deteriorated, stress-related plasma biochemical indices increased, glycolytic substrate contents decreased, glycolytic enzyme activities and product contents increased, and aerobic metabolic enzyme activities exhibited initial increases followed by declines, ATPase activities decreased, antioxidant enzyme activities decreased, and the lipid peroxidation marker contents increased. It is noteworthy that GABA treatment could avoid water quality deterioration during transportation, inhibit an elevation in stress-related biochemical indicators, regulate energy metabolism, and reduce oxidative damage in tawny puffer, especially at 50 and 150 mg/L concentrations. In summary, GABA treatment can effectively alleviate the transport stress of tawny puffer.
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BACKGROUND: Lipopolysaccharides (LPS) is well known to manifest a miscarriage-inducing effector during early pregnancy and activate macrophage to induce M1 macrophage polarization. However, the role of macrophage polarization in LPS-related miscarriage-inducing effect is not apparent. METHODS: In this work, gene expression changes and the percentage of M1/M2 macrophages and monocytes in LPS-induced miscarried uterus were firstly analyzed by RNA sequencing (RNA-seq) and Flow Cytometry. To explore the origin that contributes to M1/M2 macrophage differentiation, the expression of monocyte chemotactic protein (MCP-1), CCL3, and CCL4, chemokines related to monocyte/macrophage migration, was tested by quantitative real time PCR (qRT-PCR). RESULTS: We found that percentage of M1 macrophages rose, while the percentage of M2 macrophages declined down in the injected mice uterus. Meanwhile, the percentage of M1 and M2 macrophages showed no significant difference in the spleens of LPS injected mice compared to PBS injected control mice. Expression of Mcp-1, Ccl3, and Ccl4 and numbers of monocytes were remarkably up-regulated in LPS-induced miscarried mice uterus. CONCLUSION: These results indicated that polarization and proportion changes of macrophage in the uterus may contribute to miscarriage. Our work provides new evidence correlating the aberrant regulation of M1/M2 macrophage polarization with deleterious miscarriage-inducing effects. This will help us understand the roles of critical immune cell differentiation in maintaining normal pregnancy.
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Aborto Espontáneo , Lipopolisacáridos , Macrófagos , Útero , Femenino , Animales , Macrófagos/metabolismo , Macrófagos/inmunología , Lipopolisacáridos/farmacología , Ratones , Útero/inmunología , Útero/metabolismo , Embarazo , Aborto Espontáneo/inmunología , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Diferenciación Celular , Monocitos/metabolismo , Monocitos/inmunología , Quimiocina CCL3/metabolismo , Quimiocina CCL3/genética , Polaridad Celular , Quimiocina CCL4/metabolismo , Quimiocina CCL4/genéticaRESUMEN
Sex differences in the brain have been widely reported and may hold the key to elucidating sex differences in many medical conditions and drug response. However, the molecular correlates of these sex differences in structural and functional brain measures in the human brain remain unclear. Herein, we used sample entropy (SampEn) to quantify the signal complexity of resting-state functional magnetic resonance imaging (rsfMRI) in a large neuroimaging cohort (N = 1,642). The frontoparietal control network and the cingulo-opercular network had high signal complexity while the cerebellar and sensory motor networks had low signal complexity in both men and women. Compared with those in male brains, we found greater signal complexity in all functional brain networks in female brains with the default mode network exhibiting the largest sex difference. Using the gene expression data in brain tissues, we identified genes that were significantly associated with sex differences in brain signal complexity. The significant genes were enriched in the gene sets that were differentially expressed between the brain cortex and other tissues, the estrogen-signaling pathway, and the biological function of neural plasticity. In particular, the G-protein-coupled estrogen receptor 1 gene in the estrogen-signaling pathway was expressed more in brain regions with greater sex differences in SampEn. In conclusion, greater complexity in female brains may reflect the interactions between sex hormone fluctuations and neuromodulation of estrogen in women. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09954-y.
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Cellular behavior is regulated by mechanical signals within the cellular microenvironment. Additionally, changes of temperature, blood flow, and muscle contraction also affect cellular state and the development of diseases. In clinical practice, physical therapy techniques such as ultrasound, vibration, exercise, cold therapy, and hyperthermia are commonly employed to alleviate pain and treat diseases. However, the molecular mechanism about how these physiotherapy methods stimulate local tissues and control gene expression remains unknow. Fortunately, the discovery of YAP filled this gap, which has been reported has the ability to sense and convert a wide variety of mechanical signals into cell-specific programs for transcription, thereby offering a fresh perspective on the mechanisms by which physiotherapy treat different diseases. This review examines the involvement of Hippo/YAP signaling pathway in various diseases and its role in different physical therapy approaches on diseases. Furthermore, we explore the potential therapeutic implications of the Hippo/YAP signaling pathway and address the limitations and controversies surrounding its application in physiotherapy.
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BACKGROUND AND AIM: Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle-bone unit in PTOA studies remains unclear. METHODS: Eighteen 8-week-old Sprague-Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia. RESULTS: Eight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action. CONCLUSION: Treadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle-bone unit.
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Enfermedades Óseas Metabólicas , Osteoartritis , Ratas , Animales , Fibronectinas , Mioquinas , Ratas Sprague-Dawley , Fibras Musculares Esqueléticas , Osteoartritis/etiología , AtrofiaRESUMEN
OBJECTIVES: In view of the serious ageing of China's population and the low desire of elderly people to purchase institutionalised elderly care services, we explored the willingness of Chinese elderly people to purchase institutionalised elderly care services and its influencing factors. DESIGN: This was a cross-sectional study. Three multivariate logistic regression analysis models of the willingness of elderly people to purchase institutionalised elderly care services were established (model 1: 'reluctance - willingness'; model 2: 'reluctance - hesitation'; and model 3: 'hesitation - willingness') to explore the factors that influence elderly people's willingness to purchase institutionalised elderly care services. SETTING: This study was based on the 2022 Psychology and Behaviour Investigation of Chinese Residents database. PARTICIPANTS: Research data from 4123 older adults who met the requirements of this study were screened from the database. RESULTS: Of the 4123 respondents, roughly equal numbers had negative and positive attitudes towards purchasing institutionalised senior care services (1125, 27.3% vs 1079, 26.2%, respectively), and 1919 (46.5%) had hesitant attitudes. The analysis of model 1 showed that medical insurance participation, the number of children and siblings, chronic diseases and per capita monthly household income had an influential effect on the willingness of elderly people to purchase institutional care. In model 2, we found that factors such as per capita monthly household income and anxiety led to hesitancy among older adults to purchase institutionalised senior care services. In model 3, we further found that social support and health literacy led to a shift from hesitation to willingness to purchase institutionalised elderly care services. CONCLUSION: The number of children, number of siblings, per capita monthly income of the family, medical insurance participation, health status, health literacy and social support were found to be the main factors influencing the purchase of institutionalised care by elderly individuals.
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Envejecimiento , Renta , Niño , Humanos , Anciano , Estudios Transversales , Estado de Salud , China , Encuestas y CuestionariosRESUMEN
Cisplatin resistance remains a persistent challenge in cervical cancer (CC) treatment. Molecular biomarkers have garnered attention for their association with cisplatin resistance in various diseases. Long non-coding RNAs (lncRNAs) exert significant influence on CC development. This study explores the role of LOC644656 in regulating cisplatin resistance in CC. Parental and cisplatin-resistant CC cells underwent cisplatin treatment. Functional assays assessed cell proliferation and apoptosis under different conditions. RNA pull-down with mass spectrometry, along with literature review, elucidated the interaction between LOC644656, ZNF143, and E6-AP. Mechanistic assays analyzed the relationship between different factors. RT-qPCR and western blot quantified RNA and protein levels, respectively. In vivo models validated E6-AP's function. Results revealed LOC644656 overexpression in cisplatin-resistant CC cells, exacerbating cell growth. LOC644656 recruited ZNF143 to activate E6-AP transcription, promoting cisplatin resistance in CC. In conclusion, LOC644656 positively modulates E6-AP expression via ZNF143-mediated transcriptional activation, contributing to cisplatin resistance in CC.
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Cisplatino , Resistencia a Antineoplásicos , MicroARNs , Transactivadores , Ubiquitina-Proteína Ligasas , Neoplasias del Cuello Uterino , Femenino , Humanos , Línea Celular Tumoral , Proliferación Celular , Cisplatino/uso terapéutico , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , ARN , Transactivadores/metabolismo , Activación Transcripcional , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Macrocyclic lactones such as abamectin and ivermectin constitute an important class of broad-spectrum insecticides. Widespread resistance to synthetic insecticides, including abamectin and ivermectin, poses a serious threat to the management of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), a major pest of cruciferous plants worldwide. P-glycoprotein (Pgp), a member of the ABC transporter superfamily, plays a crucial role in the removal of amphiphilic xenobiotics, suggesting a mechanism for drug resistance in target organisms. In this study, PxPgp1, a putative Pgp gene from P. xylostella, was cloned and characterized. The open reading frame (ORF) of PxPgp1 consists of 3774 nucleotides, which encodes a 1257-amino acid peptide. The deduced PxPgp1 protein possesses structural characteristics of a typical Pgp, and clusters within the insect ABCB1. PxPgp1 was expressed throughout all developmental stages, and showed the highest expression level in adult males. PxPgp1 was highly expressed in midgut, malpighian tubules and testes. Elevated expression of PxPgp1 was observed in P. xylostella strains after they were exposed to the abamectin treatment. In addition, the constitutive expressions of PxPgp1 were significantly higher in laboratory-selected and field-collected resistant strains in comparison to their susceptible counterpart.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Clonación Molecular , Resistencia a los Insecticidas/genética , Mariposas Nocturnas/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/química , Secuencia de Aminoácidos , Animales , Insecticidas/envenenamiento , Ivermectina/análogos & derivados , Ivermectina/envenenamientoRESUMEN
Railway ballast layer is an indispensable component of railway transport. Ballast morphology plays an important effect in ballast-sleeper interaction and the durability of ballast layer. In this study, four types of ballast with different morphological parameters were generated and discrete element method was adopted to investigate the direct shear behaviors. The initial packing states were studied by analyzing the porosities and the normal contact force distributions. The shear results were verified by the reported testing results. On the other hand, one-way ANOVA tests were performed to explore the impact of ballast shape on the initial packing behaviors and the direct shear performance. Results indicated that for all four parameters, aspect ratio (AR), sphericity (Φ), roundness (RD) and convexity (CON), the initial porosities decreased first and increased subsequently along with the increase of the parameters. The four parameters could significantly affect the internal friction inside the assemblies. For each parameter, the larger the parameter, the insignificant the internal friction effect. One-way ANOVA tests revealed that all the four parameters were significant in affecting the initial porosities and the internal friction. Moreover, during the direct shear process, the larger the AR or Φ, the smaller the coordination number, which was mainly ascribed to the ballast shapes.
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Introduction: Subjective cognitive decline (SCD) with a positive amyloid burden has been recognized as the earliest clinical symptom of the preclinical phase of Alzheimers disease (AD), providing invaluable opportunities to improve our understanding of the natural history of AD and determine strategies for early therapeutic interventions. Methods: The microstructure of white matter in patients showing SCD in the preclinical phase of AD (SCD of pre-AD) was evaluated using diffusion images, and voxel-wise fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusivities were assessed and compared among participant groups. Significant clusters in the tracts were extracted to determine their associations with alterations in the cognitive domains. Results: We found that individuals with SCD of pre-AD may have subclinical episodic memory impairment associated with the global amyloid burden. Meanwhile, we found significantly reduced FA and λ1 in the right cingulum (cingulate and hippocampus) in AD dementia, while significantly increased FA and decreased MD as well as λ23 in the SCD of pre-AD group in comparison with the HC group. Discussion: In conclusion, increased white matter microstructural integrity in the right cingulum (cingulate and hippocampus) may indicate compensation for short-term episodic memory in individuals with SCD of pre-AD in comparison with individuals with AD and healthy elderly individuals.