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Radiation-tolerance and repairable flexible transistors and integrated circuits (ICs) with low power consumption have become hot topics due to their wide applications in outer space, nuclear power plants, and X-ray imaging. Here, we designed and developed novel flexible semiconducting single-walled carbon nanotube (sc-SWCNT) thin-film transistors (TFTs) and ICs. Sc-SWCNT solid-electrolyte-gate dielectric (SEGD) TFTs showcase symmetric ambipolar characteristics with flat-band voltages (VFB) of â¼0 V, high ION/IOFF ratios (>105), and the recorded irradiation resistance (up to 22 Mrad). Moreover, flexible sc-SWCNT ICs, including CMOS-like inverters and NAND and NOR logic gates, have excellent operating characteristics with low power consumption (≤8.4 pW) and excellent irradiation resistance. Significantly, sc-SWCNT SEGD TFTs and ICs after radiation with a total irradiation dose (TID) ≥ 11 Mrad can be repaired after thermal heating at 100 °C. These outstanding characteristics are attributed to the designed device structures and key core materials including SEGD and sc-SWCNT.
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BACKGROUND: Ketone ß-hydroxybutyrate (BHB) has been reported to prevent tumor cell proliferation and improve drug resistance. However, the effectiveness of BHB in oxaliplatin (Oxa)-resistant colorectal cancer (CRC) and the underlying mechanism still require further proof. METHODS: CRC-Oxa-resistant strains were established by increasing concentrations of CRC cells to Oxa. CRC-Oxa cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) were checked following BHB intervention in vitro. The subcutaneous and metastasis models were established to assess the effects of BHB on the growth and metastasis of CRC-Oxa in vivo. Eight Oxa responders and seven nonresponders with CRC were enrolled in the study. Then, the serum BHB level and H3K79me, H3K27ac, H3K14ac, and H3K9me levels in tissues were detected. DOT1L (H3K79me methyltransferase) gene knockdown or GNE-049 (H3K27ac inhibitor) use was applied to analyze further whether BHB reversed CRC-Oxa resistance via H3K79 demethylation and/or H3K27 deacetylation in vivo and in vitro. RESULTS: Following BHB intervention based on Oxa, the proliferation, migration, invasion, and EMT of CRC-Oxa cells and the growth and metastasis of transplanted tumors in mice were suppressed. Clinical analysis revealed that the differential change in BHB level was associated with drug resistance and was decreased in drug-resistant patient serum. The H3K79me, H3K27ac, and H3K14ac expressions in CRC were negatively correlated with BHB. Furthermore, results indicated that H3K79me inhibition may lead to BHB target deletion, resulting in its inability to function. CONCLUSIONS: ß-hydroxybutyrate resensitized CRC cells to Oxa by suppressing H3K79 methylation in vitro and in vivo.
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Ácido 3-Hidroxibutírico , Proliferación Celular , Neoplasias Colorrectales , Resistencia a Antineoplásicos , Histonas , Oxaliplatino , Oxaliplatino/farmacología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Humanos , Ácido 3-Hidroxibutírico/farmacología , Animales , Ratones , Histonas/metabolismo , Metilación , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Masculino , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Movimiento Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones DesnudosRESUMEN
OBJECTIVE: Cemiplimab, a novel PD-1 inhibitor, exhibits significant antitumor activity against advanced non-small cell lung cancer (NSCLC). However, the cost-effectiveness of this drug for the treatment remains unclear. This study aimed to assess the cost-effectiveness of cemiplimab plus chemotherapy compared to chemotherapy for the treatment of advanced NSCLC, from the perspective of the United States payer. METHODS: A partitioned survival approach was developed to project the disease progression of NSCLC. Overall survival (OS) and progression-free survival (PFS) data were obtained from the EMPOWER lung 3 trial and extrapolated to estimate long-term survival outcomes. Direct medical costs and utility data were collected. The primary outcome measure, the incremental cost-utility ratio (ICUR), was used to evaluate the cost-effectiveness of cemiplimab plus chemotherapy regimen. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of the results. RESULTS: In the base-case analysis, the ICUR for cemiplimab plus chemotherapy versus chemotherapy alone was estimated to be $395,593.8 per quality-adjusted life year (QALY). OWSA revealed that the results were sensitive to Hazard ratio value, utility of PFS, and cost of cemiplimab. PSA demonstrated that cemiplimab plus chemotherapy exhibited 0% probability of cost-effectiveness.In hypothetical scenario analysis, the ICUR of two regimens was $188.803.3/QALY. OWSA revealed that the results were sensitive to the discount rate, utility, and cost of cemiplimab. PSA indicated that cemiplimab plus chemotherapy achieved at least an 11.5% probability of cost-effectiveness. CONCLUSION: Our cost-effectiveness analysis suggests that, at its current price, cemiplimab plus chemotherapy regimen is unlikely to be a cost-effective option compared with chemotherapy alone for advanced NSCLC patients, based on a threshold of $150,000 per QALY, from the perspective of the US payer.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Estados Unidos , Carcinoma de Pulmón de Células no Pequeñas/patología , Análisis Costo-Beneficio , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica , Años de Vida Ajustados por Calidad de VidaRESUMEN
This study aimed to elucidate the opioid mechanisms underlying dexamethasone-induced pain antihypersensitive effects in neuropathic rats. Dexamethasone (subcutaneous and intrathecal) and membrane-impermeable Dex-BSA (intrathecal) administration dose-dependently inhibited mechanical allodynia and thermal hyperalgesia in neuropathic rats. Dexamethasone and Dex-BSA treatments increased expression of dynorphin A in the spinal cords and primary cultured microglia. Dexamethasone specifically enhanced dynorphin A expression in microglia but not astrocytes or neurons. Intrathecal injection of the microglial metabolic inhibitor minocycline blocked dexamethasone-stimulated spinal dynorphin A expression; intrathecal minocycline, the glucocorticoid receptor antagonist Dex-21-mesylate, dynorphin A antiserum, and κ-opioid receptor antagonist GNTI completely blocked dexamethasone-induced mechanical antiallodynia and thermal antihyperalgesia. Additionally, dexamethasone elevated spinal intracellular cAMP levels, leading to enhanced phosphorylation of PKA, p38 MAPK and CREB. The specific adenylate cyclase inhibitor DDA, PKA inhibitor H89, p38 MAPK inhibitor SB203580 and CREB inhibitor KG-501 completely blocked dexamethasone-induced anti-neuropathic pain and increased microglial dynorphin A exprression. In conclusion, this study reveal that dexamethasone mitigateds neuropathic pain through upregulation of dynorphin A in spinal microglia, likely involving the membrane glucocorticoid receptor/cAMP/PKA/p38 MAPK/CREB signaling pathway.
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Proteínas Quinasas Dependientes de AMP Cíclico , AMP Cíclico , Dexametasona , Dinorfinas , Microglía , Neuralgia , Ratas Sprague-Dawley , Transducción de Señal , Médula Espinal , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , AMP Cíclico/metabolismo , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos , Masculino , Neuralgia/metabolismo , Neuralgia/tratamiento farmacológico , Dinorfinas/metabolismo , Ratas , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Dexametasona/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Hiperalgesia/metabolismo , Hiperalgesia/tratamiento farmacológicoRESUMEN
A brief, practical catalytic process for the production of optically active γ-functionalized alcohols from relevant alkenes has been developed by using a robust Mn(III)/air/(Me2SiH)2O catalytic system combined with lipase-catalyzed kinetic resolution. This approach demonstrates exceptional tolerance toward proximal functional groups present on alkenes, enabling the achievement of high yields and exclusive enantioselectivity. Under this sequential catalytic system, the chiral alkene precursors can also be converted into γ-functionalized alcohols and related acetates as separable single enantiomers.
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In our previous study, a screening of a variety of lycotonine-type diterpenoid alkaloids were screened for cardiotonic activity revealed that lycoctonine had moderate cardiac effect. In this study, a series of structurally diverse of lycoctonine were synthesized by modifying on B-ring, D-ring, E-ring, F-ring, N-atom or salt formation on lycoctonine skeleton. We evaluated the cardiotonic activity of the derivatives by isolated frog heart, aiming to identify some compounds with significantly enhanced cardiac effects, among which compound 27 with a N-isobutyl group emerged as the most promising cardiotonic candidate. Furthermore, the cardiotonic mechanism of compound 27 was preliminarily investigated. The result suggested that the cardiotonic effect of compound 27 is related to calcium channels. Patch clamp technique confirmed that the compound 27 had inhibitory effects on CaV1.2 and CaV3.2, with inhibition rates of 78.52 % ± 2.26 % and 79.05 % ± 1.59 % at the concentration of 50 µM, respectively. Subsequently, the protective effect of 27 on H9c2 cells injury induced by cobalt chloride was tested. In addition, compound 27 can alleviate CoCl2-induced myocardial injury by alleviating calcium overload. These findings suggest that compound 27 was a new structural derived from lycoctonine, which may serve as a new lead compound for the treatment of heart failure.
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Aconitina/análogos & derivados , Alcaloides , Cardiotónicos , Cardiotónicos/farmacología , Aconitina/química , Alcaloides/farmacología , Alcaloides/química , Canales de Calcio , CalcioRESUMEN
The integration of silicon waveguides with low-dimensional materials with excellent optoelectronic properties can enable compact and highly integrated optical devices with multiple advantages for multiple fields. A carbon nanotube (CNT) photodetector integrated on the silicon waveguide has the potential to meet on-chip high-speed optical interconnection systems, based on the outstanding properties of CNTs such as picosecond-level intrinsic photoresponse time, high charge carrier mobility, broad spectral response, high absorption coefficient, and so on. However, the thermal stability of the device may be compromised due to the local suspension in the channel for the height difference between the WG and the substrate. Here, we report a low-cost and low-optical-loss method to achieve the planarized silicon waveguide. After that, the CNT photodetectors integrated on the original and planarized waveguide with asymmetric palladium (Pd)-hafnium (Hf) metal contacts are fabricated. The influence of this planarization method on the performance of devices is analyzed via comparing the dark leakage current, the leakage current rectification ratio (CRR), the series resistances (R S), and the photoelectric response. Finally, a CNT photodetector based on the planarized waveguide with a photocurrent (I p h ) â¼510.84n A, a photoresponsivity (R I) â¼51.04m A/W, the dark current â¼0.389µA, as well as a 3 dB bandwidth â¼34G H z at the large reverse voltage -3V is shown.
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Manganese is essential trace elements, to participate in the body a variety of biochemical reactions, has important physiological functions, such as stimulate the immune cell proliferation, strengthen the cellular immunity, etc. However, excessive manganese exposure can cause damage to multiple systems of the body.The immune system is extremely vulnerable to external toxicants, however manganese research on the immune system are inadequate and biomarkers are lacking. Therefore, here we applied a manganese-exposed rat model to make preliminary observations on the immunotoxic effects of manganese. We found that manganese exposure inhibited humoral immune function in rats by decreasing peripheral blood IgG (ImmunoglobulinG, IgG), IgM (ImmunoglobulinM, IgM) and complement C3 levels; It also regulates rat cellular immune activity by influencing peripheral blood, spleen, and thymus T cell numbers and immune organ ICs (Immune Checkpoints, ICs) and cytokine expression. Furthermore, it was revealed that the impact of manganese exposure on the immune function of rats exhibited a correlation with both the dosage and duration of exposure. Notably, prolonged exposure to high doses of manganese had the most pronounced influence on rat immune function, primarily manifesting as immunosuppression.The above findings suggest that manganese exposure leads to impaired immune function and related changes in immune indicators, or may provide clues for the discovery of its biomarkers.
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Manganeso , Linfocitos T , Ratas , Animales , Manganeso/toxicidad , Inmunoglobulina M , Inmunoglobulina G , BiomarcadoresRESUMEN
BACKGROUND: Researchers have made great efforts to help parents of children with intellectual disabilities overcome the stress and burden. Learning to be resilient is one effective strategy. AIM: This study explores resilience among parents of children with intellectual disabilities and how career burnout and self-regulation relate to parents' resilience in mainland China. METHODS: The Burnout Scale, the Self-Regulation Scale and the Resilience Scale were administered to 324 parents of children with intellectual disabilities. RESULTS: Results showed that career burnout significantly negatively influenced resilience (ß = -0.269, p = 0.000), while self-regulation significantly positively influenced resilience (ß = 0.754, p = 0.000). In addition, self-regulation moderated the relationships between career burnout and resilience (ß = 0.176, p = 0.003). CONCLUSION: The findings offer valuable insights for enhancing the resilience of parents of children with intellectual disabilities.
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Discapacidad Intelectual , Padres , Resiliencia Psicológica , Autocontrol , Humanos , Discapacidad Intelectual/psicología , Masculino , Femenino , Padres/psicología , Adulto , Niño , China , Agotamiento Psicológico/psicología , Persona de Mediana Edad , Adolescente , Encuestas y Cuestionarios , Adaptación PsicológicaRESUMEN
Acoustic tomography utilizes sensor arrays to collect sound wave signals, enabling non-contact measurement of physical parameters within an area of interest. Compared to optical technologies, acoustic tomography offers the advantages of low cost, low maintenance, and easy installation. Current research in acoustic tomography mainly focuses on reconstruction algorithms for temperature fields, while monitoring the composition and concentration of gases is significant for ensuring safety and improving efficiency, such as in scenarios like boiler furnaces and aviation engine nozzles. In excitable gases, the speed of sound exhibits an S-shaped curve that changes with frequency, a characteristic that could be potentially useful for acoustic tomography. Therefore, this study primarily discusses the quantitative calculation of gas concentration and temperature based on the dispersion of the speed of sound. By employing graphic processing and pattern matching methods, a coupled relationship of the dispersion of the speed of sound with gas concentration and temperature is established. The projection intersection method is used to calculate the concentration and temperature of binary and ternary gas mixtures. Combined with the inversion method, a joint reconstruction method for gas concentration fields and temperature fields based on the dispersion of the speed of sound is developed. The feasibility of the proposed simultaneous reconstruction method for temperature and concentration fields is validated using numerical simulations. Additionally, an acoustic tomography experimental system was set up to conduct reconstruction experiments for binary gas concentration fields and temperature fields, confirming the effectiveness of the proposed method.
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This research examined the effects of principal transformational leadership on teachers' inclusive teaching behaviour, with a particular inquiry into the mediating effects of teachers' inclusive role identity and efficacy for inclusive practice, as informed by identity theory and social cognitive theory. Structural equation modelling with bootstrapping estimation was conducted using data from 712 teachers delivering inclusive teaching in primary or secondary schools in China. The results revealed the sequentially mediating mechanisms of teachers' inclusive role identity and efficacy underlying the principal transformational leadership effects on teachers' inclusive teaching behaviour. Research implications are also discussed.
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Background: Fine particulate matter (PM2.5), an important component of ambient air pollution, induces significant adverse health effects. MitoQuinone (MitoQ), a mitochondria-targeted antioxidant, has been reported to play a protective role in various diseases. However, the roles of MitoQ in PM2.5 induced pulmonary toxicity remains to be elucidated. Methods: All the experiments were performed at Higher Educational Key Laboratory for Translational Oncology of Fujian Province, Putian City, China in 2023. Pulmonary epithelial cells (A549) were pretreated with 4 µM MitoQ for 2 h and exposed to PM2.5 for 24 h. Cell viability was tested through CCK8 assay. Oxidative stress state and active mitochondria was used to study MitoQ's effect on PM2.5 induced injury, and cell apoptosis was measured using a flow cytometer and analyzed by Bcl-2 family. Results: MitoQ pretreatment significantly relieved a decreased cell viability, subsequently, MitoQ alleviated ROS production and prevented the reduction of T-AOC and GSH and increased the expression of NF-E2-related factor 2 (Nrf2) and p62 in A549 cells exposed to PM2.5. MitoQ restored the decreased mitochondrial dysfunction and dynamics disorder and inhibited activated mitochondrial-mediated apoptosis induced by PM2.5. Furthermore, the decreased ratio of Bcl-2/Bax and expression of Mcl-1 and the enhanced expression of Caspase-3 were reversed by MitoQ pretreatment. Conclusion: MitoQ might be regarded as a potential drug to relieve PM2.5 induced pulmonary epithelial cells damage.
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It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in three nonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.
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Obesidad , Paladar Blando , Apnea Obstructiva del Sueño , Porcinos Enanos , Lengua , Animales , Porcinos , Apnea Obstructiva del Sueño/fisiopatología , Lengua/fisiopatología , Paladar Blando/fisiopatología , Obesidad/fisiopatología , Obesidad/complicaciones , Obesidad/patología , Fenómenos Biomecánicos , Electromiografía , Respiración , MasculinoRESUMEN
Degradation of shoots, characterized by stunted growth and signs of water deficit, is common in bamboo stands. However, the specific mechanisms underlying water utilization in degrading shoots remain unclear. This study sought to address this gap by harvesting bamboo shoots and culms of Phyllostachys edulis 'Pachyloen', employing cytological and physiological techniques to compare water utilization mechanisms between healthy and degrading shoots, and investigating the water supply to bamboo shoots by the parent bamboo. The water pressure in the degrading shoots was markedly lower compared to that of the healthy shoots, and it declined as the degradation progressed, resulting in reduced water content and the cessation of guttation in the degrading shoots. In conditions of water deficit, the percentage of free water in bamboo shoots decreased while the percentages of bound and semi-bound water increased, with the proportion of semi-bound water reaching as high as 88.13% in the late stages of degradation. The water potential of parent bamboo culms of different ages varied at different times of the day and during different growth stages of bamboo shoots, showing a strong association with the development of bamboo shoots. Conversely, the correlation between changes in the water potential of bamboo shoots and their degradation patterns was found to be comparatively minimal. The weakening of the connection between the bamboo shoots and the parent bamboo culms may play a significant role in the degradation of the bamboo shoots. This is evidenced by a decrease in the fluorescence intensity of the nucleus in bamboo shoots and the degradation of genetic material. This study lays the foundation for future research into the mechanisms of bamboo shoot degradation.
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The development of large-scale integration of optoelectronic neuromorphic devices with ultralow power consumption and broadband responses is essential for high-performance bionics vision systems. In this work, we developed a strategy to construct large-scale (40 × 30) enhancement-mode carbon nanotube optoelectronic synaptic transistors with ultralow power consumption (33.9 aJ per pulse) and broadband responses (from 365 to 620 nm) using low-work function yttrium (Y)-gate electrodes and the mixture of eco-friendly photosensitive Ag2S quantum dots (QDs) and ionic liquids (ILs)-cross-linking-poly(4-vinylphenol) (PVP) (ILs-c-PVP) as the dielectric layers. Solution-processable carbon nanotube thin-film transistors (TFTs) showed enhancement-mode characteristics with the wide and controllable threshold voltage window (-1 Vâ¼0 V) owing to use of the low-work-function Y-gate electrodes. It is noted that carbon nanotube optoelectronic synaptic transistors exhibited high on/off ratios (>106), small hysteresis and low operating voltage (≤2 V), and enhancement mode even under the illumination of ultraviolet (UV, 365 nm), blue (450 nm), and green (550 nm) to red (620 nm) pulse lights when introducing eco-friendly Ag2S QDs in dielectric layers, demonstrating that they have the strong fault-tolerant ability for the threshold voltage drifts caused by various manufacturing scenarios. Furthermore, some important bionic functions including a high paired pulse facilitation index (PPF index, up to 290%), learning and memory function with the long duration (200 s), and rapid recovery (2 s). Pavlov's dog experiment (retention time up to 20 min) and visual memory forgetting experiments (the duration of high current for 180 s) are also demonstrated. Significantly, the optoelectronic synaptic transistors can be used to simulate the adaptive process of vision in varying light conditions, and we demonstrated the dynamic transition of light adaptation to dark adaptation based on light-induced conditional behavior. This work undoubtedly provides valuable insights for the future development of artificial vision systems.
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Toxoplasma gondii is an obligate intracellular parasite of phylum Apicomplexa that poses a huge threat to pregnant hosts, and induces tragic outcomes for pregnant hosts, fetuses and newborns. However, the molecular mechanism underlying the tragic consequences caused by T. gondii remains to be revealed. In the present study, we applied RNA-seq to study the transcriptomic landscape of the whole reproductive organ of pregnant mice post T. gondii infection, aiming to reveal the key altered biological characters of reproductive organs of pregnant mice that could contribute to the tragic outcomes caused by T. gondii infection. The results of the present study showed that the transcriptome of reproductive organs of pregnant mice was significantly altered by T. gondii infection. A total of 2,598 differentially expressed genes (DEGs) were identified, including 1,449 upregulated genes and 1,149 downregulated genes. Enrichment analysis of the DEGs showed that the significantly altered features of reproductive organs of pregnant mice were excessive inflammatory responses, downregulated metabolism processes, and congenital diseases. The chemotaxis of immune cells in the reproductive organs of infected pregnant mice could also be reshaped by 19 differentially expressed chemokines and 6 differentially expressed chemokine receptors that could contribute to the damages of reproductive organ in pregnant mice. Overall, the findings of present study may help to understand the pathogenic mechanism of the acute T. gondii infection in reproductive organs of pregnant mice, and it could also help to improve toxoplasmosis therapeutics for pregnant individuals.
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Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits.
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Biomarcadores , Eritrocitos , Manganeso , Síndromes de Neurotoxicidad , Animales , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Manganeso/sangre , Manganeso/toxicidad , Manganeso/orina , Biomarcadores/sangre , Biomarcadores/orina , Masculino , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/sangre , Ratas , Humanos , Intoxicación por Manganeso/sangre , Ratas Sprague-Dawley , Exposición Profesional/efectos adversos , FemeninoRESUMEN
BACKGROUND: Toxoplasma gondii, a globally distributed zoonotic obligate intracellular parasite, infects a wide array of mammals, including humans, sheep, and birds. As a unique sheep breed in southwestern China, Yunnan semi-fine wool sheep occupies an important position in animal husbandry in Zhaotong due to its strong adaptability, high reproductive rate, and excellent wool quality. Lambs infected with T. gondii are prone to neurological symptoms and growth retardation, while T. gondii infection in ewes can cause abortions, stillbirths, and deformities, thus affecting sheep reproduction and sheep product quality. Meanwhile, mutton and dairy products contaminated with T. gondii can become potential sources of human infection, potentially threatening public health and safety. METHOD: To understand the T. gondii infection in semi-fine wool sheep in Zhaotong, Yunnan Province, 586 blood samples were collected and subjected to indirect hemagglutination assay (IHA) for T. gondii antibodies, and the infection-related factors were analyzed through cross-sectional analysis. In the meantime, nested PCR was conducted on a total of 217 samples collected from 31 rodents caught in and around the sheep breeding ground to test the T. gondii B1 gene in rodent tissues. RESULTS: A total of 94 sera tested positive for T. gondii antibodies, with a total positive rate of 16.04% (94/586) (95% CI: 14.77-20.89). Cross-sectional statistical analysis on factors related to semi-fine wool sheep infection rate, including sampling season, sex, age, and weight, suggested that age (< 6 months: 23.81%; 6-12 months: 11.74%; > 12 months: 15.83%) was a significant factor explaining the infection rate differences (P = 0.003 < 0.05, χ2 = 11.62, df = 2). Thus, age was considered a key risk factor for T. gondii infection in this study (odds ratio, OR = 2.35, 95% CI: 1.42-3.87). Nested PCR analysis on 217 (heart, liver, spleen, lung, kidney, brain, and muscle) tissues from the 31 rodents indicated that 11 tested positive. The total infection rate of rodents in and around the breeding ground was 35.48% (11/31), and 14 samples tested positive, with a positive infection rate of 6.45% (14/217). CONCLUSION: The T. gondii infection rates of semi-fine wool sheep and rodents from their breeding environment in Zhaotong, Yunnan Province, were high, necessitating enhanced prevention, control, and treatment measures to ensure the healthy breeding of semi-fine wool sheep and veterinary public health and safety.
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Diabetes mellitus (DM) is a serious chronic metabolic disease that can lead to many serious complications, such as cardiovascular disease, retinopathy, neuropathy, and kidney disease. Once diagnosed with diabetes, patients need to take oral hypoglycemic drugs or use insulin to control blood sugar and slow down the progression of the disease. This has a significant impact on the daily life of patients, requiring constant monitoring of the side effects of medication. It also imposes a heavy financial burden on individuals, their families, and even society as a whole. Adipose-derived stem cells (ADSCs) have recently become an emerging therapeutic modality for DM and its complications. ADSCs can improve insulin sensitivity and enhance insulin secretion through various pathways, thereby alleviating diabetes and its complications. Additionally, ADSCs can promote tissue regeneration, inhibit inflammatory reactions, and reduce tissue damage and cell apoptosis. The potential mechanisms of ADSC therapy for DM and its complications are numerous, and its extensive regenerative and differentiation ability, as well as its role in regulating the immune system and metabolic function, make it a powerful tool in the treatment of DM. Although this technology is still in the early stages, many studies have already proven its safety and effectiveness, providing new treatment options for patients with DM or its complications. Although based on current research, ADSCs have achieved some results in animal experiments and clinical trials for the treatment of DM, further clinical trials are still needed before they can be applied in a clinical setting.
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Diabetes Mellitus Experimental , Animales , Humanos , Diabetes Mellitus Experimental/metabolismo , Tejido Adiposo , Adipocitos/metabolismo , Glucemia/metabolismo , Células Madre/metabolismoRESUMEN
As the latest and most anticipated method of tumor immunotherapy, CAR-NK therapy has received increasing attention in recent years, and its safety and high efficiency have irreplaceable advantages over CAR-T. Current research focuses on the application of CAR-NK in hematological tumors, while there are fewer studies on solid tumor. This article reviews the process of constructing CAR-NK, the effects of hypoxia and metabolic factors, NK cell surface receptors, cytokines, and exosomes on the efficacy of CAR-NK in solid tumor, and the role of CAR-NK in various solid tumor. The mechanism of action and the research status of the potential of CAR-NK in the treatment of solid tumor in clinical practice, and put forward the advantages, limitations and future problems of CAR-NK in the treatment of solid tumor.