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Dendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive. Here, through analyzing publicly available databases, we observe substantial alterations in NAM levels and NAM metabolic pathways during DCs activation. Furthermore, we discover that NAM, but not Nicotinamide Mononucleotide (NMN), significantly inhibits DCs over-activation in vitro and in vivo. The suppression of DCs hyperactivation effectively alleviates symptoms of psoriasis. Mechanistically, NAM impairs DCs activation through a Poly (ADP-ribose) polymerases (PARPs)-NF-κB dependent manner. Notably, phosphoribosyl transferase (NAMPT) and PARPs are significantly upregulated in lipopolysaccharide (LPS)-stimulated DCs and psoriasis patients; elevated NAMPT and PARPs expression in psoriasis patients correlates with higher psoriasis area and severity index (PASI) scores. In summary, our findings underscore the pivotal role of NAM in modulating DCs functions and autoimmune disorders. Targeting the NAMPT-PARP axis emerges as a promising therapeutic approach for DC-related diseases.
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Enfermedades Autoinmunes , Células Dendríticas , Niacinamida , Nicotinamida Fosforribosiltransferasa , Poli(ADP-Ribosa) Polimerasas , Psoriasis , Transducción de Señal , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Células Dendríticas/inmunología , Niacinamida/farmacología , Humanos , Transducción de Señal/efectos de los fármacos , Animales , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Psoriasis/metabolismo , Enfermedades Autoinmunes/tratamiento farmacológico , Nicotinamida Fosforribosiltransferasa/metabolismo , Ratones , Poli(ADP-Ribosa) Polimerasas/metabolismo , FN-kappa B/metabolismo , Ratones Endogámicos C57BL , LipopolisacáridosRESUMEN
BACKGROUND: Lymphoma has become 1 of the 10 most common cancers with increased prevalence in young- and middle-aged adults in China. This poses a tremendous burden on patients and their families and brings great challenges to maintaining the balance of family functioning in young- and middle-aged patients. OBJECTIVE: This cross-sectional study aimed to analyse the influence of resourcefulness on the family functioning of Chinese young- and middle-aged lymphoma patients. METHODS: A total of 172 Chinese young- and middle-aged patients with lymphoma were recruited from the oncology departments of two tertiary hospitals in Zhengzhou, Henan, China. They were invited to complete a survey that included a demographic questionnaire, the Resourcefulness Scale and the Chinese Version Family Adaptability and Cohesion Scale II. Multiple linear regression was used to analyse the related factors for family functioning. RESULTS: The multiple regression analysis revealed that the main influencing factors of family cohesion were resourcefulness (ßâ =â 0.338, 95% CI (0.072, 0.173)), spouse caregiver (ßâ =â 0.376, 95% CI (1.938, 10.395)), and cancer stage (ßâ =â -0.274, 95% CI (-3.219, -1.047)). Resourcefulness (ßâ =â 0.438, 95% CI (0.096, 0.181)), spouse caregiver (ßâ =â 0.340, 95% CI (1.348, 8.363)), and family per capita monthly income (ßâ =â 0.157, 95% CI (0.066, 2.243)) were the influencing factors of family adaptability. CONCLUSIONS: Healthcare professionals and family scholars should value young- and middle-aged lymphoma patients' family functioning throughout the cancer treatment process, and family interventions should be designed by healthcare providers based on patients' resourcefulness. Moreover, healthcare providers need to pay attention to the risk factors of patients' family cohesion and adaptability, such as low family per capita monthly income, and consider employing corresponding measures to help them.
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Cuidadores , Linfoma , Humanos , Estudios Transversales , China , Masculino , Femenino , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Linfoma/psicología , Cuidadores/psicología , Relaciones Familiares , Adaptación Psicológica , Familia/psicología , Adulto JovenRESUMEN
OBJECTIVE: Investigation of the effects of 5-5- (4-N, N-diacetoxylphenyl)-10,15,20- tetraphenylporphyrin (DTPP)-mediated photodynamic therapy (PDT) on oxidative stress and mitochondrial apoptosis in LA795 lung cancer cells. METHODS: Proteomics was used to identify differentially expressed proteins after PDT treatment. The apoptosis rate was determined by flow cytometry. Morphologic observation of apoptosis, reactive oxygen species (ROS) levels, antioxidant indices, nitric oxide (NO) content, mitochondrial membrane potential (MMP), and Caspase- 9 and Caspase-3 were determined by assays; apoptosis-related protein levels of Cytochrome (Cyto) c, Bcl- 2, Bax were determined by Western blot. RESULTS: Typical apoptosis morphology of LA795 cells was observed after PDT. The cells were mainly in the apoptosis death pathway with high cell apoptosis rates. The proteomics study observed the apoptosis-associated proteins, oxidative stress proteins, antioxidant proteins, the cytoskeletal protein and mitochondrial dysfunction in LA 795 cells. Additional results indicated that PDT could increase levels of ROS, NO; decrease glutathione (GSH) content and MMP; upregulated Bax, Cyto c, and Caspase-3 protein expression, inhibited Bcl-2 protein expression, and further induced cell apoptosis. The effect of DTPP-PDT on lung cancer was: first, mitochondrial Cyto c is released into the cytoplasm, then Caspase- 9 / Caspase-3 was activated, Bcl-2 decreased/Bax increased, initiating cell apoptosis. CONCLUSION: DTPP-PDT could induce oxidative stress and apoptosis via mitochondrial pathways in LA795 cells.
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Neoplasias Pulmonares , Compuestos Organofosforados , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Caspasa 3/metabolismo , Fotoquimioterapia/métodos , Proteína X Asociada a bcl-2/metabolismo , Especies Reactivas de Oxígeno , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Estrés Oxidativo , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
BACKGROUND: Analyse and discuss the immediate stability of the cervical spine after anterior cervical discectomy and fusion using a door-shaped titanium plate and compare it with the traditional titanium plate, to provide biomechanical evidence for the rationality and effectiveness of the door-shaped titanium plate in clinical applications. METHODS: Ten adult goat C4/5 vertebral bodies were obtained, and models were prepared using denture base resin. Biomechanical experiments were performed on the specimens before internal fixation. MTS was used to conduct non-destructive biomechanical loading tests in six directions, including flexion, extension, left-right bending, and left-right torsion, recording the range of motion (ROM) and neutral zone (NZ) of each specimen. The specimens were then randomly divided into two groups: the study group was fixed with a door-shaped titanium plate, and the control group was fixed with a traditional titanium plate. ROM and NZ in each direction were measured again. After measurements, both groups were subjected to 0.5 Hz torsion loading with a torque of 2 N m for a total of 3000 cycles, followed by measuring ROM and NZ in six directions once more. RESULTS: Compared to before fixation, ROM and NZ in both groups significantly decreased in all six directions after fixation, with statistical significance (P < 0.05); after fixation, the study group showed slightly lower values for various mechanical reference parameters compared to the control group, with no statistical significance (P > 0.05); after 3000 torsional loads, both internal fixation groups showed increased ROM and NZ compared to after fixation but to a lower extent, and no screw or titanium plate loosening was observed. Compared to before fixation, the differences were still statistically significant (P < 0.05), with the study group having slightly lower ROM and NZ values in all directions compared to the control group, with no statistical significance (P > 0.05). CONCLUSION: The door-shaped titanium plate exhibits mechanical properties similar to the traditional titanium plate in all directions, and its smaller size and simpler surgical operation can be used for anterior cervical endoscopic surgery, reducing surgical trauma. It is clinically feasible and deserves further research and promotion.
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Fusión Vertebral , Titanio , Animales , Fenómenos Biomecánicos , Placas Óseas , Vértebras Cervicales/cirugía , Discectomía , Cabras , Rango del Movimiento Articular , Modelos AnimalesRESUMEN
BACKGROUND: Cancer is highly prevalent worldwide. Family resilience is a positive variable that helps families burdened by advanced cancer to cope effectively. This study aimed to describe the family resilience of advanced cancer patients and caregivers in dyads and identify its influencing factors at the individual and dyadic levels. METHODS: This multisite cross-sectional study was conducted in oncology units in five tertiary hospitals in China. A total of 270 advanced cancer patient-caregiver dyads were recruited between June 2020 and March 2021. Patients' and caregivers' family resilience was measured by the Family Resilience Assessment Scale. Data on potential influencing factors, including demographic and disease-related characteristics as well as family sense of coherence, psychological resilience, perceived social support, symptom burden, and caregiver burden, were collected. Multilevel modeling analysis was adopted to control for the interdependence of the dyads. RESULTS: A total of 241 dyads were included in the data analysis. The mean ages of patients and caregivers were 53.96 (SD 15.37) and 45.18 (SD 13.79) years, respectively. Most caregivers were spouses and adult children (45.6% and 39.0%, respectively). Patients reported a higher mean family resilience score than caregivers (152.56 vs. 149.87, respectively). Undergoing fewer than two types of treatment and a lower symptom burden of patients predicted higher patient (B = -9.702, -0.134, respectively) and caregiver (B = -5.462, -0.096, respectively) family resilience. Patients also reported higher family resilience under the following conditions: 1) were on a medical insurance plan other than the new rural cooperative medical system (B = 6.089), 2) had a better family sense of coherence (B = 0.415), 3) whose caregivers were unmarried (B = 8.618), perceived lower social support (B = -0.145) and higher psychological resilience (B = 0.313). Caregivers who were ≤ 44 years old (B = -3.221), had similar previous caregiving experience (B = 7.706), and had a stronger family sense of coherence (B = 0.391) reported higher family resilience. CONCLUSIONS: Our findings highlight the importance of adopting a dyadic approach when caring for advanced cancer patients and their caregivers. Dyadic longitudinal research is suggested to discover more modifiable factors of family resilience and tailored interventions are needed to obtain optimal dyadic outcomes.
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Neoplasias , Resiliencia Psicológica , Adulto , Humanos , Adolescente , Cuidadores/psicología , Adaptación Psicológica , Salud de la Familia , Estudios Transversales , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias/psicología , Calidad de Vida/psicología , Familia/psicologíaRESUMEN
Background: Chemotherapy often negatively impacts the nutritional status of breast cancer patients, and healthy dietary behaviors are important for patient wellbeing. With the guidance of the "Knowledge, Attitude and Practice model" (KAP model), the objective of this survey was to determine the frequency with which patients engage in healthy dietary behaviors and to explore the association between healthy dietary behaviors and nutrition literacy and dietary attitudes. Methods: This study included a total of 284 breast cancer patients undergoing chemotherapy from three hospitals spanning three cities in China. Face-to-face interviews were conducted to collect demographic and clinical characteristics as well as the Dietary Nutritional Knowledge, Attitude and Practice Questionnaire (DNKAPQ) and the Nutrition Literacy Measurement Scale for Chinese Adult (NLMS-CA). Results: Participants exhibited medium to high scores for nutrition literacy, dietary attitude and dietary behavior. Nutrition literacy (r = 0.505, p < 0.001) and dietary attitude (r= 0.326, p < 0.001) scores were both positively correlated with the total dietary behavior score. The total nutrition literacy score was positively correlated with the total dietary behavior score (r = 0.286, p < 0.001). In the univariate analysis, age, body mass index, living environment, education level, monthly family income, work status, menopausal status, number of comorbidities, relapse and endocrine therapy were significantly associated with dietary behavior (p < 0.05). In the multiple linear regression analysis, patients' dietary behavior was significantly associated with nutrition literacy (ß = 0.449, p < 0.001) and dietary attitude (ß = 0.198, p < 0.001). These two factors accounted for 28.6% of the variation in the patients' dietary behavior scores. Conclusion: There is an important need for targeted dietary and nutritional interventions designed and implemented by health professionals to improve dietary behaviors. Intervention design and content should take the patients' nutrition literacy and dietary attitudes into consideration. In particular, women who are older, overweight, unemployed, and postmenopausal and live in rural areas, exhibit fewer comorbidities, have a lower family income and education level, have not relapsed and are currently receiving endocrine therapy are in urgent need of diet-specific intervention.
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PURPOSE: Breast cancer patients undergoing chemotherapy experience adverse reactions, which lead to poor nutritional status. The objective of this study was to explore the dietary practice of Chinese breast cancer patients undergoing chemotherapy and to analyse the influence of nutrition literacy, self-care self-efficacy and perceived social support on dietary practice. METHOD: A total of 295 participants from three hospitals in China were enrolled. The Dietary Nutritional Knowledge, Attitude and Practice Questionnaire; Nutrition Literacy Measurement Scale for Chinese Adults; Strategies Used by People to Promote Health and Perceived Social Support Scale were administered. Multiple linear regressions were used to identify influencing factors. RESULTS: The dietary practice of patients were generally satisfactory. Nutrition literacy (r = 0.460, p < 0.001), self-care self-efficacy (r = 0.513, p < 0.001) and perceived social support (r = 0.703, p < 0.001) were positively correlated with dietary practice. The main factors influencing participants' dietary practice were nutrition literacy, self-care self-efficacy, perceived social support, living environment, cancer stage, body mass index, chemotherapy cycle and average monthly household income (all p < 0.05). The model explained 59.0% of the variance in dietary practice. CONCLUSIONS: Health professionals should emphasize breast cancer patients' dietary practice throughout the entire chemotherapy course, and dietary interventions should be designed by oncology nurses based on patients' nutrition literacy, self-care self-efficacy and perceived social support. Female patients who have a higher body mass index and income, live in rural areas, have a lower education level, have stage I cancer and have undergone numerous chemotherapy cycles are the focus population of intervention.
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Neoplasias de la Mama , Estado Nutricional , Adulto , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Autoeficacia , Promoción de la Salud , Autocuidado , Apoyo SocialRESUMEN
A simple template strategy was applied to prepare a Fe, N co-doped hollow carbon (Fe-NHC) nanoreactor for the oxygen reduction reaction (ORR) by coating Fe nanoparticles (Fe-NPs) with polydopamine (PDA), followed by high temperature pyrolysis and acid-leaching. With this method, Fe-NPs were used as both the template and the metal precursor, so that the nanoreactors can preserve the original spherical morphology and embed Fe single atoms on the inner walls. The carbonized PDA contained abundant N content, offering an ideal coordination environment for Fe atoms. By regulating the mass ratio of Fe-NPs and PDA, an optimal sample with a carbon layer thickness of 12 nm (Fe-NHC-3) was obtained. The hollow spherical structure of the nanoreactors and the atomically dispersed Fe were verified by various physical characterizations. As a result, Fe-NHC-3 performed well in ORR tests under alkaline conditions, with high catalytic activity, durability, and methanol resistance, demonstrating that the as-fabricated materials have the potential to be applied in the cathodic catalysis of fuel cells.
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OBJECTIVE: To explore the clinical efficacy of posterior percutaneous endoscopic discectomy(PPECD) in the treatment of cervical spondylotic radiculopathy. METHODS: A total of 56 patiens with single segment cervical spondylotic radiculopathy from December 2017 to October 2020, were randomly divided into observation group and control group. In observation group, there were 16 males and 11 females, including 8 cases of C4,5, 13 cases of C5,6 and 6 cases of C6,7 performed posterior percutaneous endoscopic discectomy, aged from 34 to 61 years old with an average of (51.15±6.29) years old. In control group, there were 19 males and 10 females with single segment cervical spondylotic radiculopathy including 10 cases of C4,5, 14 cases of C5,6 and 5 cases of C6,7 performed anterior cervical discectomy and fusion, aged from 40 to 65 years old with an average of (53.24±5.31) years old. The operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were recorded. Visual analogue scale(VAS) and neck disability index(NDI) were used to evaluate the clinical efficacy. Cervical plain films or MRIs, CTs were taken for re-visiting patients. RESULTS: All patients were followed up more than 2 years. The observation group patients were followed up, the duration ranged from 24 to 42 months with an average of (30.48±4.91) months. The control group patients were followed up, the duration ranged from 25 to 47 months, with an average of (32.76±4.53) months. Compared with control group, operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were decreased(P<0.05). Compared with pre-operation, VAS of neck and upper limb and NDI at the latest follow-up between two groups were significantly improved(P<0.05). Compared with control group, VAS of neck and upper limb at 1 day after operation in observation group were significantly reduced(P<0.05). There was no significant difference in VAS of neck and upper limb and NID at 1, 3 months and the latest follow-up after operation between two groups(P>0.05). In the observation group, one patient's deltoid muscle strength was weakened to grade 4 after operation, and returned to normal after 12 weeks of conservative treatment. In control group, there was 1 case of postoperative adjacent spondylosis with symptoms of spinal compression after 2 years operation, then underwent cervical artificial intervertebral disc replacement. And there was 1 case of dysphagia after operation in control group and improved after 1 year. There was no significant difference in incidence of complications between two groups. CONCLUSION: PPECD has advantages of shortening operative time, decreasing intraoperative blood loss, reducing postoperative time of lying in bed and length of postoperative hospital stay. However, applicable age range of patients and long-term clinical efficacy needs further study.
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Radiculopatía , Fusión Vertebral , Espondilosis , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Radiculopatía/cirugía , Vértebras Cervicales/cirugía , Resultado del Tratamiento , Discectomía , Espondilosis/cirugía , Pérdida de Sangre Quirúrgica , Hemorragia Posoperatoria , Estudios RetrospectivosRESUMEN
Sweet potato vine, the byproduct of sweet potato, has a high nutritional value. Silage is an effective solution for nutrient preservation. This article explored the effects of sweet potato vine silage (SPVS) supplementation on meat quality, antioxidant capacity and immune function in finishing pigs. One hundred and eighty finishing pigs (Berkshire × Licha Black) with a body weight of 74.54 ± 3.32 kg were randomly divided into three groups. The three groups were separately fed basal diet (Ctrl), Ctrl supplemented with 2.5% SPVS (LSPVS) or 5% SPVS (HSPVS) on a dry matter basis. Results showed that the eye muscle area in the LSPVS group was significantly increased. The carcass weight in the HSPVS was significantly reduced compared with Ctrl. For the meat quality, only cooking loss in both HSPVS and LSPVS was reduced while other indexes had no significant differences. For the antioxidant capacity, the hepatic level of glutathione (GSH) peroxidase (GSH-PX) was significantly upregulated in LSPVS but downregulated in HSPVS. In the serum, HSPVS decreased GSH level and increased GSH-PX level. HSPVS significantly reduced hepatic interleukin-1ß (IL-1ß) levels and LSPVS significantly reduced IL-12 levels and increased IL-8 and IL-6 levels. Moreover, HSPVS and LSPVS promoted the secretion of immunoglobulin M (IgM) and IgG in the serum. Our data showed that low-dose SPVS supplementation improved carcass traits and high-dose SPVS supplementation increased immune function in finishing pigs, which provides a new alternative to improve animal health.
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Antioxidantes , Ipomoea batatas , Porcinos , Animales , Ensilaje , Alimentación Animal/análisis , Suplementos Dietéticos , Carne/análisis , Glutatión , InmunidadRESUMEN
Ensemble feature selection (EFS) has attracted significant interest in the literature due to its great potential in reducing the discovery rate of noise features and stabilizing the feature selection results. In view of the superior performance of block-regularized m × 2 cross-validation on generalization performance and algorithm comparison, a novel EFS technology based on block-regularized m × 2 cross-validation is proposed in this study. Contrary to the traditional ensemble learning with a binomial distribution, the distribution of feature selection frequency in the proposed technique is approximated by a beta distribution more accurately. Furthermore, theoretical analysis of the proposed technique shows that it yields a higher selection probability for important features, lower selected risk for noise features, more true positives, and fewer false positives. Finally, the above conclusions are verified by the simulated and real data experiments.
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As a theoretically rigorous and accurate method, FEP-ABFE (Free Energy Perturbation-Absolute Binding Free Energy) calculations showed great potential in drug discovery, but its practical application was difficult due to high computational cost. To rapidly discover antiviral drugs targeting SARS-CoV-2 Mpro and TMPRSS2, we performed FEP-ABFE-based virtual screening for â¼12,000 protein-ligand binding systems on a new generation of Tianhe supercomputer. A task management tool was specifically developed for automating the whole process involving more than 500,000 MD tasks. In further experimental validation, 50 out of 98 tested compounds showed significant inhibitory activity towards Mpro, and one representative inhibitor, dipyridamole, showed remarkable outcomes in subsequent clinical trials. This work not only demonstrates the potential of FEP-ABFE in drug discovery but also provides an excellent starting point for further development of anti-SARS-CoV-2 drugs. Besides, â¼500 TB of data generated in this work will also accelerate the further development of FEP-related methods.
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In order to discover more promising anti-fungal agents, a series of benzoxazole family was synthesized by PPA-catalyzed condensation and a Raney nickel/hydrazine reduction. Altogether 45 compounds were obtained in good to excellent yields and characterized by FT-IR, NMR, MS, and X-ray crystal diffraction. Moreover, the biological activity against eight phytopathogenic fungi was investigated. All in all, most of these compounds bear moderate antifungal activities. Among them, three candidates show the strongest activities, compound 4ac, 4bc provided over 50% inhibition rate against five fungi. Especially, the inhibitory rate of compound 4ah on Mycosphaerella melonis reached 76.4%.
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Antifúngicos , Benzoxazoles , Benzoxazoles/química , Relación Estructura-Actividad , Espectroscopía Infrarroja por Transformada de Fourier , Antifúngicos/química , Hongos , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Urban agglomeration will be the main mode of future urbanization in China, greatly influencing social and economic development and ecosystem protection at the whole city cluster scale. It is important to analyze the impacts of large-scale, scattered land use and cover change (LUCC) consisting of one-pole-multi-point urbanization in city clusters on regional ecosystem services (ESs), so as to increase ecological security and maintain ES levels. Using the urban-rural gradient analysis method (UGAM), this study examined driver-response mechanisms of large-scale, scattered agglomeration urbanization on ESs along an urban-rural gradient and at a regional scale. This was done by simulating and analyzing tempo-spatial variations in ES characteristics along concentric ring gradients in the Central Yunnan City Cluster (CYCC) under its present urbanization path. The results showed that rapid urban sprawl is the main driver affecting the integral value of ESs in CYCC and that ES trade-offs (through LUCC caused by urbanization) between adjacent zones along the urban-rural gradient will particularly exacerbate the degradation of integral ES levels. Hence, CYCC should follow a sustainable, eco-friendly urbanization path and consider ecological principles and the impact of LUCC on regional ESs along the urban-rural gradient in top-level design and decision-making on urban planning and strategic land use management. Differentiated regional development policies should be formulated for each area, the urban-rural development pattern and layout optimized, the scale of construction land rationally controlled, and the overall efficiency of land use improved. Ecological buffers should be set up around areas with sharp and obvious changes in land use, to alleviate the negative impact of large-scale, decentralized city cluster urbanization on regional ESs.
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Ecosistema , Urbanización , Conservación de los Recursos Naturales/métodos , China , CiudadesRESUMEN
BACKGROUND: Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic strategies. Tumor cells often undergo spontaneous apoptotic cell death in tumor microenvironment, these apoptotic cells are histologically co-localized with immunosuppressive macrophages. However, the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully understood. In this study, we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways involved. METHODS: Apoptotic cells and macrophages in tumors were detected by immunohistochemical staining. Morphological analysis was performed with Giemsa staining. Lipids generated from apoptotic cells were detected by liquid chromatography-mass spectrometry. Phosphatidylserine-containing liposomes were prepared to mimic apoptotic cells. The expression of protein was determined by real-time PCR, immunohistochemistry enzyme-linked immunosorbent assay and Western blotting. Mouse malignant ascites and subcutaneous tumor models were designed for in vivo analysis. Transgenic mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic studies. RESULTS: The location and the number of apoptotic cells were correlated with that of macrophages in several types of carcinomas. Phosphatidylserine, a lipid molecule generated in apoptotic cells, induced polarization and accumulation of M2-like macrophages in vivo and in vitro. Moreover, sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcutaneous tumor models. Further analyses suggested that phosphoserine induced a M2-like phenotype in macrophages, which was related to the activation of phosphoserine receptors including T-cell immunoglobin mucin 4 (TIM4) and the FAK-SRC-STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain-containing protein 3 (JMJD3). Administration of specific inhibitors of these pathways could reduce tumor progression. CONCLUSIONS: This study suggest that apoptotic cell-generated phosphoserine might be a notable signal for immunosuppressive macrophages in tumors, and the related pathways might be potential therapeutic targets for cancer therapy.
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Neoplasias , Fosfatidilserinas , Animales , Apoptosis , Ascitis/metabolismo , Histona Demetilasas con Dominio de Jumonji , Macrófagos/metabolismo , Ratones , Neoplasias/metabolismo , Fosfatidilserinas/metabolismo , Fosfatidilserinas/farmacología , Fosfoserina/metabolismo , Fosfoserina/farmacología , Factor de Transcripción STAT3/metabolismo , Microambiente TumoralRESUMEN
BACKGROUND: Preeclampsia (PE) is a severe hypertension-related disorder occurring during pregnancy that leads to significant mortality and morbidity in both the foetus and mother. Atractylenolide (ATL), a traditional Chinese natural agent isolated from the herb Atractylodes macrocephala, exhibits a series of pharmacological activities, including anti-oxidative stress and anti-inflammatory effects. PURPOSE: The impacts of ATL on apoptosis and oxidative stress in HTR-8/SVneo cells during PE development was investigated. STUDY DESIGN: We identified ATL by an overlap analysis of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database using the keyword 'gestational hypertension' and Traditional Chinese Medicine (Batman-TCM) database using the keyword 'Atractylodes macrocephala'. METHODS: Cell viability, proliferation, and migration were detected by CCK-8, EdU, and transwell assays. Flow cytometry and 2',7'-dichlorodihydrofluorescein diacetate were used to assess apoptosis and reactive oxygen species (ROS) levels. RESULTS: EdU and CCK-8 assays demonstrated that ATL significantly enhanced the viability of HTR-8/SVneo cells. Transwell assays showed that ATL remarkably induced the migration of HTR-8/SVneo cells. Moreover, ROS production in HTR-8/SVneo cells was induced by H2O2, whilst ATL alleviated this H2O2-induced ROS production and apoptosis in cells. CONCLUSION: ATL attenuated apoptosis and oxidative stress in HTR-8/SVneo cells in PE by activating the MAPK/ERK signalling pathway. ATL has potential to be utilized as a potential therapeutic candidate for PE.
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Preeclampsia , Apoptosis , Movimiento Celular , Femenino , Humanos , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo , Preeclampsia/metabolismo , Embarazo , Trofoblastos/metabolismoRESUMEN
BACKGROUND: Preeclampsia (PE), a serious pregnancy disorder, is responsible for maternal and fetal mortality worldwide. At present, numerous candidate biomarkers have been studied to predict PE. OBJECTIVE: To explore the role of Corin in PE risk prediction and then evaluate the predictive ability of soluble vascular endothelial growth factor receptor-1 (sFlt-1), placenta growth factor (PLGF), and sFlt-1/PLGF after the addition of Corin. METHODS: A total of 135 pregnant women from Affiliated Hospital of Shandong University of Traditional Chinese Medicine participated in this study in their first trimester. A nested case-control study was conducted and all subjects were divided into PE groups (n=46) and controls (n=89). The levels of PLGF, sFlt-1, sFlt-1/PLGF ratio, and Corin of the two groups at 12-16 weeks of gestation were measured and analyzed. Receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to evaluate the predictive ability of various biomarkers. RESULTS: The concentrations of sFlt-1, sFlt-1/PLGF, and Corin in PE group were significantly higher than that in controls, while the concentration of PLGF in the PE group was lower. The area under curve (AUC) of sFlt-1, PLGF and sFlt-1/PLGF for predicting PE was 0.786, 0.719 and 0.866, respectively. Combined with Corin, the prediction ability of the above biomarkers could be improved to 0.876, 0.847, and 0.897, respectively. Corin in combination with sFlt-1/PLGF resulted in improvements with 12.6% being reclassified and a resulting NRI of 0.142 (0.020~0.263) and IDI of 0.087 (0.037~0.137). CONCLUSION: The addition of Corin to sFlt-1, PLGF and sFlt-1/PLGF can improve the ability of each marker to predict PE risk. Corin in combination with sFlt-1/PLGF can be used as ideal markers to identify the pregnant women who subsequently develop PE, which will help in risk stratification and better therapeutic management.
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Using finite time thermodynamic theory, an irreversible steady-flow Lenoir cycle model is established, and expressions of power output and thermal efficiency for the model are derived. Through numerical calculations, with the different fixed total heat conductances (UT) of two heat exchangers, the maximum powers (Pmax), the maximum thermal efficiencies (ηmax), and the corresponding optimal heat conductance distribution ratios (uLP(opt)) and (uLη(opt)) are obtained. The effects of the internal irreversibility are analyzed. The results show that, when the heat conductances of the hot- and cold-side heat exchangers are constants, the corresponding power output and thermal efficiency are constant values. When the heat source temperature ratio (τ) and the effectivenesses of the heat exchangers increase, the corresponding power output and thermal efficiency increase. When the heat conductance distributions are the optimal values, the characteristic relationships of P-uL and η-uL are parabolic-like ones. When UT is given, with the increase in τ, the Pmax, ηmax, uLP(opt), and uLη(opt) increase. When τ is given, with the increase in UT, Pmax and ηmax increase, while uLP(opt) and uLη(opt) decrease.