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OBJECTIVE: To investigate the association between the use of proton pump inhibitors (PPIs) and overactive bladder (OAB) in adults. METHODS: This study adopts a cross-sectional approach to scrutinize data derived from the National Health and Nutrition Examination Survey (NHANES), spanning from 2007 to 2018. It employs multivariable logistic regression along with restricted cubic splines (RCS) to investigate the relationship between the use of PPI and the incidence of OAB. Additionally, through interaction and stratification analyses, the study delves into how specific factors may influence this correlation. RESULTS: A total of 24,458 adults participated in this study. Individuals using PPIs exhibited higher rates of nocturia, urge incontinence, and OAB compared to non-users. After full adjustment, PPI users had a significantly increased risk of developing OAB (OR=1.36, 95%CI: 1.17-1.60). Moreover, with each year of continued PPI usage, the frequency of OAB symptoms escalated by 3% (P = .01). Further examinations within various subgroups maintained a uniform direction in these effect estimates. CONCLUSION: The findings of this research highlight a noteworthy positive link between the use of PPIs and the emergence of OAB among adults. Moreover, it was observed that an extended period of using PPIs correlates with a heightened likelihood of encountering OAB.
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Controlling the coherence of chaotic soliton bunch holds the promise to explore novel light-matter interactions and manipulate dynamic events such as rogue waves. However, the coherence control of chaotic soliton bunch remains challenging, as there is a lack of dynamic equilibrium mechanism for stochastic soliton interactions. Here, we develop a strategy to effectively control the coherence of chaotic soliton bunch in a laser. We show that by introducing a lumped fourth-order-dispersion (FOD), the soliton oscillating tails can be formed and generate the potential barriers among the chaotic solitons. The repulsive force between neighboring solitons enabled by the potential barriers gives rise to an alleviation of the soliton fusion/annihilation from stochastic interactions, endowing the capability to control the coherence in chaotic soliton bunch. We envision that this result provides a promising test-bed for a variety of dynamical complexity science and brings new insights into the nonlinear behavior of chaotic laser sources.
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Locusta migratoria is an important phytophagous pest, and its gut microbial communities play an important role in cellulose degradation. In this study, the gut microbial and cellulose digestibility dynamics of Locusta migratoria were jointly analyzed using high-throughput sequencing and anthrone colorimetry. The results showed that the gut microbial diversity and cellulose digestibility across life stages were dynamically changing. The species richness of gut bacteria was significantly higher in eggs than in larvae and imago, the species richness and cellulose digestibility of gut bacteria were significantly higher in early larvae (first and second instars) than in late larvae (third to fifth instars), and the diversity of gut bacteria and cellulose digestibility were significantly higher in imago than in late larvae. There is a correlation between the dynamics of gut bacterial communities and cellulose digestibility. Enterobacter, Lactococcus, and Pseudomonas are the most abundant genera throughout all life stages. Six strains of highly efficient cellulolytic bacteria were screened, which were dominant gut bacteria. Carboxymethyl cellulase activity (CMCA) and filter paper activity (FPA) experiments revealed that Pseudomonas had the highest cellulase enzyme activity. This study provides a new way for the screening of cellulolytic bacteria and lays the foundation for developing insects with significant biomass into cellulose-degrading bioreactors. IMPORTANCE: Cellulose is the most abundant and cheapest renewable resource in nature, but its degradation is difficult, so finding efficient cellulose degradation methods is an urgent challenge. Locusta migratoria is a large group of agricultural pests, and the large number of microorganisms that inhabit their intestinal tracts play an important role in cellulose degradation. We analyzed the dynamics of Locusta migratoria gut microbial communities and cellulose digestibility using a combination of high-throughput sequencing technology and anthrone colorimetry. The results revealed that the gut microbial diversity and cellulose digestibility were dynamically changed at different life stages. In addition, we explored the intestinal bacterial community of Locusta migratoria across life stages and its correlation with cellulose digestibility. The dominant bacterial genera at different life stages of Locusta migratoria were uncovered and their carboxymethyl cellulase activity (CMCA) and filter paper activity (FPA) were determined. This study provides a new avenue for screening cellulolytic bacteria and lays the foundation for developing insects with significant biomass into cellulose-degrading bioreactors.
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Bactérias , Celulose , Microbioma Gastrointestinal , Locusta migratoria , Animais , Celulose/metabolismo , Microbioma Gastrointestinal/fisiologia , Locusta migratoria/microbiologia , Bactérias/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Larva/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Digestão/fisiologiaRESUMO
OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.
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Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gencitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , Adulto , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Albuminas/uso terapêutico , Idoso , Intervalo Livre de Progressão , China , Metástase NeoplásicaRESUMO
As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.
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Glucose , Moluscocidas , Caramujos , Animais , Moluscocidas/farmacologia , Caramujos/efeitos dos fármacos , Caramujos/metabolismo , Caramujos/parasitologia , Glucose/metabolismo , Água DoceRESUMO
Dissipative solitons (DSs), due to the complex interplay among dispersion, nonlinear, gain and loss, illustrate abundant nonlinear dynamics behaviors. Especially, dispersion plays an important role in the research of DS dynamics in ultrafast fiber lasers. Previous studies have mainly focused on the effect of even-order dispersion, i.e., group velocity dispersion (GVD) and fourth-order dispersion. In fact, odd-order dispersions, such as third-order dispersion (TOD), also significantly influences the dynamics of DSs. However, due to the lack of dispersion engineering tools, few experimental researches in this domain have been reported. In this work, by employing a pulse shaper in ultrafast fiber laser, an in-depth exploration of the DS dynamics influenced by TOD was conducted. With the increase of TOD value, the stable single DS undergoes a splitting into two solitons and then enters explosion state, and ultimately evolves into a chaotic state. The laser operation state is correlated to dispersion profile, which could be controlled by TOD. Here, the positive dispersion at long-wavelength side will be gradually shifted to negative dispersion by increasing the TOD, where soliton effect will drive the transitions. These findings offer valuable insights into the nonlinear dynamics of ultrafast lasers and may also foster applications involving higher-order dispersion.
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This work presents a series of novel quinoidal organic semiconductors based on diselenophene-dithioalkylthiophene (DSpDST) conjugated cores with various side-chain lengths (-thiohexyl, -thiodecyl, and -thiotetradecyl, designated DSpDSTQ-6, DSpDSTQ-10, and DSpDSTQ-14, respectively). The purpose of this research is to develop solution-processable organic semiconductors using dicyanomethylene end-capped organic small molecules for organic field effect transistors (OFETs) application. The physical, electrochemical, and electrical properties of these new DSpDSTQs are systematically studied, along with their performance in OFETs and thin film morphologies. Additionally, the molecular structures of DSpDSTQ are determined through density functional theory (DFT) calculations and single-crystal X-ray diffraction analysis. The results reveal the presence of intramolecular S (alkyl)···Se (selenophene) interactions, which result in a planar SR-containing DSpDSTQ core, thereby promoting extended π-orbital interactions and efficient charge transport in the OFETs. Moreover, the influence of thioalkyl side chain length on surface morphologies and microstructures is investigated. Remarkably, the compound with the shortest thioalkyl chain, DSpDSTQ-6, demonstrates ambipolar carrier transport with the highest electron and hole mobilities of 0.334 and 0.463 cm2 V-1 s-1 , respectively. These findings highlight the excellence of ambipolar characteristics of solution-processable OFETs based on DSpDSTQs even under ambient conditions.
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In aquatic ecosystems, light penetrating the sediment surface in shallow lakes may regulate the internal phosphorus (P) release through benthic primary production, which subsequently affects oxidation, pH levels, and alkaline phosphatase activity in the upper sediment. To study the effects of light exposure on the P dynamics at the sediment-water interface under eutrophic conditions, a two-month mesocosm experiment was conducted in twelve cement tanks (1000 L each). The tanks were equipped with Light-Emitting Diode (LED) lights, and surface sediments collected from eutrophic Lake Nanhu (China) were exposed to four different light intensities (0, 50, 100, 200 µmol m-2 s-1). The results revealed that: 1) Both the total phosphorus concentration and the phosphorus release flux from the sediment were lower in the light treatments (mean value, 0.59-0.71 mg L-1 and 0.00-0.01 mg m-2 d-1, respectively) than in the control treatment (0.77 mg L-1 and 0.01 mg m-2 d-1, respectively), indicating that light supplement could decrease the internal P release. 2) Benthic primary production promoted by light directly absorbed soluble reactive phosphorus and decreased the internal P release. The resulting improved production could also increase dissolved oxygen concentrations at the sediment-water interface, thus indirectly inhibiting internal P release. 3) The relative contributions of direct absorption and indirect inhibition on the internal P release ranged between 23% to 69% and 31% to 77% depending on the light intensity.
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Fósforo , Poluentes Químicos da Água , Fósforo/análise , Lagos , Ecossistema , Eutrofização , Sedimentos Geológicos , Água , China , Poluentes Químicos da Água/análise , Monitoramento AmbientalRESUMO
The regulation of ancillary ligands is critical to improve catalysis of Cp*Ir complexes for CO2 hydrogenation. Herein, a series of Cp*Ir complexes with N^N or N^O ancillary ligands were designed and synthesized. These N^N and N^O donors were derived from the pyridylpyrrole ligand. The solid-state structures of Cp*Ir complexes featured a pendant pyridyl group in 1-Cl and 1-SO4 and a pyridyloxy group in 2-Cl, 3-Cl, 2-SO4, and 3-SO4. These complexes were employed as catalysts for CO2 hydrogenation to formate in the presence of alkali under a pressure range of 0.1-8 MPa and temperature range of 25-120 °C. The catalytic activity of 2-SO4 with a pyridyloxy pendant group dramatically outperformed that of 1-SO4 and 3-SO4. The TOF of conversion of CO2 into formate reached 263 h-1 at 25 °C under a total pressure of 8 MPa (CO2/H2 = 1:1). The experiments and density functional theory calculations revealed that a pendant base in metal complexes plays a key role in the rate-determining heterolytic H2 splitting and enhancing the proton transfer by forming a hydrogen bonding bridge thereby improving the catalytic activity.
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Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
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Plaquetas , Neoplasias Ovarianas , Humanos , Feminino , Plaquetas/patologia , Biomarcadores Tumorais/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , ChinaRESUMO
Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation's pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.
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Antineoplásicos , Neoplasias Ovarianas , Animais , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Feminino , Humanos , Macrolídeos , Camundongos , Proteínas Quinases Ativadas por Mitógeno , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genéticaRESUMO
The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to ß-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.
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Adenocarcinoma de Pulmão , Antineoplásicos , Cisplatino , Neoplasias Nasofaríngeas , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Bufanolídeos , Proteínas de Ligação a Calmodulina , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Cadeias Pesadas de Miosina , Miosinas/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/metabolismo , Peptidase 7 Específica de Ubiquitina , beta Catenina/metabolismoRESUMO
Myeloproliferative neoplasms (MPNs) are characterized by upregulation of proinflammatory cytokines and immune dysregulation, which provide a reasonable basis for immunotherapy in patients. Megakaryocytes are crucial in the pathogenesis of primary myelofibrosis (PMF), the most clinically aggressive subtype of MPN. In this study, we aimed to explore PD-L1 (programmed death-ligand 1) expression in megakaryocytes and its clinical implications in PMF. We analyzed PD-L1 expression on megakaryocytes in PMF patients by immunohistochemistry and correlated the results with clinicopathological features and molecular aberrations. We employed a two-tier grading system considering both the proportion of cells positively stained and the intensity of staining. Among the 85 PMF patients, 41 (48%) showed positive PD-L1 expression on megakaryocytes with the immune-reactive score ranging from 1 to 12. PD-L1 expression correlated closely with higher white blood cell count (p = 0.045), overt myelofibrosis (p = 0.010), JAK2V617F mutation (p = 0.011), and high-molecular risk mutations (p = 0.045), leading to less favorable overall survival in these patients (hazard ratio 0.341, 95% CI 0.135-0.863, p = 0.023). Our study provides unique insights into the interaction between immunologic and molecular phenotypes in PMF patients. Future work to explore the translational potential of PD-L1 in the clinical setting is needed.
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Transtornos Mieloproliferativos , Mielofibrose Primária , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Humanos , Megacariócitos/metabolismo , Megacariócitos/patologia , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Mielofibrose Primária/genética , Mielofibrose Primária/metabolismoRESUMO
Modern development of flexible electronics has made use of bioelectronic materials as artificial tissue in vivo. As hydrogels are more similar to nerve tissue, functional hydrogels have become a promising candidate for bioelectronics. Meanwhile, interfacing functional hydrogels and living tissues is at the forefront of bioelectronics. The peripheral nerve injury often leads to paralysis, chronic pain, neurologic disorders, and even disability, because it has affected the bioelectrical signal transmission between the brain and the rest of body. Here, a kind of light-stimuli-responsive and stretchable conducting polymer hydrogel (CPH) is developed to explore artificial nerve. The conductivity of CPH can be enhanced when illuminated by near-infrared light, which can promote the conduction of the bioelectrical signal. When CPH is mechanically elongated, it still has high durability of conductivity and, thus, can accommodate unexpected strain of nerve tissues in motion. Thereby, CPH can better serve as an implant of the serious peripheral nerve injury in vivo, especially in the case that the length of the missing nerve exceeds 10 mm.
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Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
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Infecções por Coronavirus/mortalidade , Aprendizado de Máquina , Pandemias , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , COVID-19 , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Medição de Risco , SARS-CoV-2 , Máquina de Vetores de SuporteRESUMO
The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid-brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Encéfalo/citologia , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Fenômenos Eletromagnéticos , Plasticidade Neuronal/efeitos dos fármacos , Animais , Sinalização do Cálcio/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Nanopartículas/química , Tirosina 3-Mono-Oxigenase/metabolismo , Ondas Ultrassônicas , Tecnologia sem Fio , Peixe-ZebraRESUMO
A high-optical-resolution artificial retina system that accurately communicates with the optic nerve is the main challenge in the modern biological science and bionic field. Here, we developed a bionic artificial retina possessing phototransduction "cells" with measurements even smaller than that of the neural cells. Using the technique of micrometer processing, we constructed a pyramid-shape periodic microarray of a photoreceptor. Each "sensing cell" took advantage of polythiophene derivative/fullerene derivative (PCBM) as a photoelectric converter. Because folic acid played an essential role in eye growth, we particularly modified the polythiophene derivatives with folic acid tags. Therefore, the artificial retina could enlarge the contact area and even recognize the nerve cells to improve the consequence of nerve stimulation. We implanted the artificial retina into blinded rats' eyes. Electrophysiological analysis revealed its recovery of photosensitive function 3 months after surgery. Our work provides an innovative idea for fabricating a high-resolution bionic artificial retina system. It shows great potential in artificial intelligence and biomedicine.
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Biônica , Polímeros/química , Retina , Animais , Ácido Fólico/química , Próteses e Implantes , Ratos , Tiofenos/químicaRESUMO
A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2-deoxy-glucose (2-DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2-DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS-sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light-induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.
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Antineoplásicos/farmacologia , Desoxiglucose/farmacologia , Estresse do Retículo Endoplasmático , Luz , Microambiente Tumoral/efeitos dos fármacos , Apoptose , Terapia Combinada , Humanos , Cinética , Células MCF-7 , Nanomedicina , Necrose , Fagocitose , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de OxigênioRESUMO
The aim of the present study was to identify whether the responses of oxidative stress in zebrafish liver are similar to those in mammalians upon low doses of Cd2+ exposure in short durations. Fish were exposed to 1.78 µM Cd2+ (treatment) and 0.0 µM Cd2+ (control) for 0, 1, 3, and 6 h. The reactive oxygen species (ROS) and lipid peroxidation (LPO) of hepatic tissues significantly increased after 3 and 6 h of Cd2+ exposure, respectively. Antioxidants glutathione peroxidase (gpx1a), superoxide dismutase (sod), and catalase (cat) were up regulated after 1-3 h, and metallothionein isoforms (smtB and mt2) increased after 3-6 h of Cd2+ exposure. The caspase-3 and p53 mRNA expressions significantly increased threefolds after 1 h of Cd2+ exposure. Results confirmed that oxidative stress in the hepatic tissue was induced by Cd2+ within 3 h. However, anti-oxidative functions immediately up regulated, causing cell apoptosis levels to decrease after 6 h of Cd2+ exposure.