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1.
Toxicol Lett ; 400: 42-48, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39117293

RESUMO

Ochratoxin A (OTA), as one of the most important and harmful mycotoxins, is classed as possible human carcinogen (group 2B). As we all know, DNA damage may cause genomic instability, cell cycle disorder, activation of DNA damage pathway, and stimulation of DNA repair system. To explore the roles of DNA damage repair protein (hMLH1) on OTA-induced G2 arrest, the DNA damage, chromosome aberration, cell cycle distribution and p53-p21 signaling pathway were evaluatd after different time OTA exposure (6, 12, 24, 48 h) in immortalized human gastric epithelial cells (GES-1). Our results demonstrated that OTA exposure could trigger genomic instability, DNA damage and G2 phase arrest of GES-1 cells. At the same time, OTA treatment could increase the expression of hMLH1, and induce phosphorylation of the p53 protein, as well as p21, in response to DNA damage. Finally, inhibition of hMLH1 by siRNA effectively prevented the activation of p53-p21 signaling pathway and rescued the G2 arrest elicited by OTA. This study demonstrated that hMLH1-p53-p21 signaling pathway played an important role in DNA damage and G2 cell cycle arrest the mediated by OTA in GES-1 cells.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21 , Dano ao DNA , Pontos de Checagem da Fase G2 do Ciclo Celular , Mucosa Gástrica , Proteína 1 Homóloga a MutL , Ocratoxinas , Transdução de Sinais , Proteína Supressora de Tumor p53 , Ocratoxinas/toxicidade , Humanos , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Transdução de Sinais/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Linhagem Celular , Instabilidade Genômica/efeitos dos fármacos , Fosforilação
2.
Cell Biosci ; 14(1): 94, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026356

RESUMO

BACKGROUD: Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. METHODS: RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. RESULTS: A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. CONCLUSIONS: In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

3.
Pestic Biochem Physiol ; 202: 105914, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879295

RESUMO

Indoor cases of Tetranychus cinnabarinus displaying resistance have been documented, but the resistance level in field populations remains unexplored in China. This study delves into the resistance dynamics of T. cinnabarinus to fenpropathrin in various field populations across China, a pressing concern in contemporary agricultural pest control. The conventional bioassay and amplicon sequencing reveal a notable absence of significant fenpropathrin resistance in field populations, contrasting with known resistance in indoor cases. Current study highlights the limitations of traditional bioassays in detecting early-stage resistance and underscores the nuanced capabilities and constraints of amplicon sequencing in resistance gene frequency analysis. By employing an integrated approach, we combined dose-response bioassays, amplicon sequencing, and statistical modeling to assess resistance levels and investigate underlying genetic factors. The model with empirical data indicates that a 5% mutation frequency represents the threshold before resistance emerges. However, the detection of the kdr mutation in certain populations ranging from 0 to 1.2%, signals an early looming threat of future resistance emergence. Additionally, we further assessed a specific dsRNA targeting VGSC genes at two concentrations (10 ng/µL and 100 ng/µL), both inducing substantial mortality by silencing target genes effectively. The exploration of RNA interference (RNAi) as a novel, more environmentally friendly pest control measure opens new avenues, despite the ongoing challenge of resistance evolution. Overall, this study underscores the necessity for evolving pest management strategies, integrating advanced biotechnological approaches with traditional methods, to effectively counter pesticide resistance and ensure sustainable agricultural productivity.


Assuntos
Resistência a Inseticidas , Piretrinas , Interferência de RNA , Tetranychidae , Animais , Tetranychidae/genética , Tetranychidae/efeitos dos fármacos , Piretrinas/farmacologia , Resistência a Inseticidas/genética , Inseticidas/farmacologia
4.
Adv Mater ; 36(32): e2405030, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38808576

RESUMO

Neuromorphic visual systems can emulate biological retinal systems to perceive visual information under different levels of illumination, making them have considerable potential for future intelligent vehicles and vision automation. However, the complex circuits and high operating voltages of conventional artificial vision systems present great challenges for device integration and power consumption. Here, bioinspired synaptic transistors based on organic single crystal phototransistors are reported, which exhibit excitation and inhibition synaptic plasticity with time-varying. By manipulating the charge dynamics of the trapping centers of organic crystal-electret vertical stacks, organic transistors can operate below 1 V with record high on/off ratios close to 108 and sharp switching with a subthreshold swing of 59.8 mV dec-1. Moreover, the approach offers visual adaptation with highly localized modulation and over 98.2% recognition accuracy under different illumination levels. These bioinspired visual adaptation transistors offer great potential for simplifying the circuitry of artificial vision systems and will contribute to the development of machine vision applications.

5.
J Cancer Res Clin Oncol ; 150(4): 211, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662258

RESUMO

BACKGROUND: Circular ribose nucleic acids (circRNAs), an abundant type of noncoding RNAs, are widely expressed in eukaryotic cells and exert a significant impact on the initiation and progression of various disorders, including different types of cancer. However, the specific role of various circRNAs in colorectal cancer (CRC) pathology is still not fully understood. METHODS: The initial step involved the use of quantitative reverse transcription polymerase chain reaction (RT-qPCR) to assess the expression levels of circRNAs and messenger RNA (mRNA) in CRC cell lines and tissues. Subsequently, functional analyses of circCOL1A1 knockdown were conducted in vitro and in vivo through cell counting kit (CCK)-8, colony formation and transwell assays, as well as xenograft mouse model of tumor formation. Molecular expression and interactions were investigated using luciferase reporter assays, Western blot analysis, RNA immunoprecipitation (RIP), and immunohistochemical staining. RESULTS: The RT-qPCR results revealed elevated levels of circCOL1A1 expressions in CRC tissues and cell lines as compared to the normal counterparts. In addition, circCOL1A1 expression level was found to be correlated with TNM stage, lymph node metastases, distant metastases, and invasion. Knockdown of circCOL1A1 resulted in impaired invasion, migration, and proliferation of CRC cells, and suppressed tumor generation in the animal model. We further demonstrated that circCOL1A1 could act as a sponge for miR-214-3p, suppressing miR-214-3p activity and leading to the upregulation of GLS1 protein to promote glutamine metabolism. CONCLUSION: These findings suggest that circCOL1A1 functions as an oncogenic molecule to promote CRC progression via miR-214-3p/GLS1 axis, hinting on the potential of circCOL1A1 as a therapeutic target for CRC.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais , Glutaminase , Glutamina , MicroRNAs , Invasividade Neoplásica , RNA Circular , Regulação para Cima , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Glutaminase/genética , Glutaminase/metabolismo , Glutamina/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , RNA Circular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Adv Mater ; 36(26): e2401821, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38567884

RESUMO

In the era of the Internet and the Internet of Things, display technology has evolved significantly toward full-scene display and realistic display. Incorporating "intelligence" into displays is a crucial technical approach to meet the demands of this development. Traditional display technology relies on distributed hardware systems to achieve intelligent displays but encounters challenges stemming from the physical separation of sensing, processing, and light-emitting modules. The high energy consumption and data transformation delays limited the development of intelligence display, breaking the physical separation is crucial to overcoming the bottlenecks of intelligence display technology. Inspired by the biological neural system, neuromorphic technology with all-in-one features is widely employed across various fields. It proves effective in reducing system power consumption, facilitating frequent data transformation, and enabling cross-scene integration. Neuromorphic technology shows great potential to overcome display technology bottlenecks, realizing the full-scene display and realistic display with high efficiency and low power consumption. This review offers a comprehensive summary of recent advancements in the application of neuromorphic technology in displays, with a focus on interoperability. This work delves into its state-of-the-art designs and potential future developments aimed at revolutionizing display technology.

7.
Phytother Res ; 38(6): 2860-2874, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38558446

RESUMO

Bone is one of the most frequent sites for metastasis in breast cancer patients. Bone metastasis significantly reduces the survival time and the life quality of breast cancer patients. Germacrone (GM) can serve humans as an anti-cancer and anti-inflammation agent, but its effect on breast cancer-induced osteolysis remains unclear. This study aims to investigate the functions and mechanisms of GM in alleviating breast cancer-induced osteolysis. The effects of GM on osteoclast differentiation, bone resorption, F-actin ring formation, and gene expression were examined in vitro. RNA-sequencing and Western Blot were conducted to explore the regulatory mechanisms of GM on osteoclastogenesis. The effects of GM on breast cancer-induced osteoclastogenesis, and breast cancer cell malignant behaviors were also evaluated. The in vivo efficacy of GM in the ovariectomy model and breast cancer bone metastasis model with micro-CT and histomorphometry. GM inhibited osteoclastogenesis, bone resorption and F-actin ring formation in vitro. Meanwhile, GM inhibited the expression of osteoclast-related genes. RNA-seq analysis and Western Blot confirmed that GM inhibited osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways. The in vivo mouse osteoporosis model further confirmed that GM inhibited osteolysis. In addition, GM suppressed the capability of proliferation, migration, and invasion and promoted the apoptosis of MDA-MB-231 cells. Furthermore, GM could inhibit MDA-MB-231 cell-induced osteoclastogenesis in vitro and alleviate breast cancer-associated osteolysis in vivo human MDA-MB-231 breast cancer bone metastasis-bearing mouse models. Our findings identify that GM can be a promising therapeutic agent for patients with breast cancer osteolytic bone metastasis.


Assuntos
Neoplasias da Mama , NF-kappa B , Osteoclastos , Osteogênese , Osteólise , Transdução de Sinais , Animais , Osteólise/tratamento farmacológico , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Osteogênese/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Sesquiterpenos de Germacrano/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Diferenciação Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células RAW 264.7
8.
Exp Hematol Oncol ; 13(1): 31, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475936

RESUMO

Sarcoma is a malignant tumor that originates from mesenchymal tissue. The common treatment for sarcoma is surgery supplemented with radiotherapy and chemotherapy. However, patients have a 5-year survival rate of only approximately 60%, and sarcoma cells are highly resistant to chemotherapy. Ferroptosis is an iron-dependent nonapoptotic type of regulated programmed cell death that is closely related to the pathophysiological processes underlying tumorigenesis, neurological diseases and other conditions. Moreover, ferroptosis is mediated via multiple regulatory pathways that may be targets for disease therapy. Recent studies have shown that the induction of ferroptosis is an effective way to kill sarcoma cells and reduce their resistance to chemotherapeutic drugs. Moreover, ferroptosis-related genes are related to the immune system, and their expression can be used to predict sarcoma prognosis. In this review, we describe the molecular mechanism underlying ferroptosis in detail, systematically summarize recent research progress with respect to ferroptosis application as a sarcoma treatment in various contexts, and point out gaps in the theoretical research on ferroptosis, challenges to its clinical application, potential resolutions of these challenges to promote ferroptosis as an efficient, reliable and novel method of clinical sarcoma treatment.

9.
Nano Lett ; 24(14): 4132-4140, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38534013

RESUMO

Inspired by the retina, artificial optoelectronic synapses have groundbreaking potential for machine vision. The field-effect transistor is a crucial platform for optoelectronic synapses that is highly sensitive to external stimuli and can modulate conductivity. On the basis of the decent optical absorption, perovskite materials have been widely employed for constructing optoelectronic synaptic transistors. However, the reported optoelectronic synaptic transistors focus on the static processing of independent stimuli at different moments, while the natural visual information consists of temporal signals. Here, we report CsPbBrI2 nanowire-based optoelectronic synaptic transistors to study the dynamic responses of artificial synaptic transistors to time-varying visual information for the first time. Moreover, on the basis of the dynamic synaptic behavior, a hardware system with an accuracy of 85% is built to the trajectory of moving objects. This work offers a new way to develop artificial optoelectronic synapses for the construction of dynamic machine vision systems.

10.
Nat Commun ; 15(1): 740, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38272878

RESUMO

Reservoir computing has attracted considerable attention due to its low training cost. However, existing neuromorphic hardware, focusing mainly on shallow-reservoir computing, faces challenges in providing adequate spatial and temporal scales characteristic for effective computing. Here, we report an ultra-short channel organic neuromorphic vertical transistor with distributed reservoir states. The carrier dynamics used to map signals are enriched by coupled multivariate physics mechanisms, while the vertical architecture employed greatly increases the feedback intensity of the device. Consequently, the device as a reservoir, effectively mapping sequential signals into distributed reservoir state space with 1152 reservoir states, and the range ratio of temporal and spatial characteristics can simultaneously reach 2640 and 650, respectively. The grouped-reservoir computing based on the device can simultaneously adapt to different spatiotemporal task, achieving recognition accuracy over 94% and prediction correlation over 95%. This work proposes a new strategy for developing high-performance reservoir computing networks.

11.
J Am Chem Soc ; 146(3): 1806-1812, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38193677

RESUMO

Controllable fluorocarbon chain elongation (CFCE) is a promising yet underdeveloped strategy for the well-defined synthesis of structurally novel polyfluorinated compounds. Herein, the direct and efficient trifluorovinylation and pentafluorocyclopropylation of aldehydes are described by using TMSCF2Br (TMS = trimethylsilyl) as the sole fluorocarbon source, accomplishing the goals of CFCE from C1 to C2 and from C1 to C3, respectively. The key to the success of these CFCE processes lies in the unique and diversified chemical reactivity of TMSCF2Br, which can serve as two different precursors, namely, a TMSCF2 radical precursor and a difluorocarbene precursor. Various functional groups are amenable to this new synthetic protocol, providing streamlined access to a broad range of alcohols containing trifluorovinyl or pentafluorocyclopropyl moieties from abundantly available aldehydes. The potential utility of these methods is further demonstrated by the gram-scale synthesis, derivatization, and measurement of log P values of the products.

12.
Ecotoxicol Environ Saf ; 270: 115868, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38142590

RESUMO

Ochratoxin A (OTA) is a mycotoxin commonly found in several food commodities worldwide with potential nephrotoxic, hepatotoxic and carcinogenic effects. We previously showed for the first time that OTA treatment enhanced glycolysis in human gastric epithelium (GES-1) cells in vitro. Here, we found that OTA exposure activated inflammatory responses, evidenced by increasing of NF-κB signaling pathway-related protein (p-p65 and p-IκBα) expressions and elevating of inflammatory cytokine (IL-1ß and IL-6) mRNA expressions in GES-1 cells. To elucidate the role of glycolysis in inflammatory effects triggered by OTA, we pretreated GES-1 cells with glycolysis inhibitor (2-deoxy-D-glucose, 2-DG) before OTA exposure. The result showed that 2-DG reduced the protein expressions of p-p65 and p-IκBα and alleviated the mRNA expressions of inflammatory cytokines in OTA-treated GES-1 cells. Furthermore, OTA activated the mTOR/HIF-1α pathway by increasing the protein expressions of p-mTOR, p-eIF4E and HIF-1α, and inhibition of mTOR with rapamycin or silencing HIF-1α with siRNA significantly attenuated OTA-enhanced glycolysis by reducing glycolysis related genes and thereby decreasing inflammatory effects of GES-1 cells. These results demonstrate that OTA activates inflammatory responses in GES-1 cells and this is controlled by mTOR/HIF-1α pathway-mediated glycolysis enhancement. Our findings provide a novel mechanistic view into OTA-induced gastric cytotoxicity.


Assuntos
Ocratoxinas , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Inibidor de NF-kappaB alfa , Linhagem Celular , Serina-Treonina Quinases TOR/genética , Glicólise , RNA Mensageiro , Epitélio
13.
Math Biosci Eng ; 20(9): 15781-15808, 2023 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-37919989

RESUMO

In the fight against the COVID-19 pandemic, China has long adhered to the "Dynamic Zero COVID-19" strategy till the end of 2022. To understand the mechanism of this strategy, we used the case of the Yangzhou summer outbreak in 2021 and a multi-stage dynamical model incorporating city-wide and key area testing-trace-isolation (TTI) strategies. We defined two time-varying indexes for measuring the disease transmission risk and the public health prevention and control force, respectively, which allowed us to explore the mechanisms of TTI policies. Integrating with the historical data and literature parameter values, we first estimated the parameters and then quantified the relevant indexes over time. The findings showed that multiple rounds of rapid testing were one of the critical measures to overcome the outbreak in Yangzhou within one month. In addition, we compared the impact of the duration of the free transmission stage, tracking rate, testing interval and precise division of key areas on the epidemiological indicators, including the final sizes of infections and isolations, peak value, peak arrival time and epidemic duration and the minimum round of testing. Our results suggest that the early detection of the epidemic, an improved efficiency of tracking, and a reduced duration of each test play a positive role in restraining COVID-19; however, a considerable investment of resources was essential to achieve a significant effect quickly.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Pandemias/prevenção & controle , Surtos de Doenças/prevenção & controle , Políticas , China/epidemiologia
14.
Sci Rep ; 13(1): 18069, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872217

RESUMO

Anoikis is a specific form of programmed cell death induced by the loss of cell contact with the extracellular matrix and other cells, and plays an important role in organism development, tissue homeostasis, disease development and tumor metastasis. We comprehensively investigated the expression patterns of anoikis-related genes (ARGs) in kidney renal clear cell carcinoma (KIRC) from public databases. Anoikis-related prognostic signatures were established based on four ARGs expression, in which KIRC patients were assigned different risk scores and divided into two different risk groups. In addition, four ARGs expression was validated by qRT-PCR. A better prognosis was observed in the low-risk group, but with lower immune activity (including immune cells and immune-related functions) in the tumor microenvironment. Combined with the relevant clinical characteristics, a nomogram for clinical application was established. Receiver operating characteristics (ROC) and calibration curves were constructed to demonstrate the predictive power of this risk signature. In addition, higher risk scores were significantly and positively correlated with higher gene expression of tumor mutation load (TMB), immune checkpoints (ICPs) and mismatch repair (MMR)-related proteins in general. The results also suggested that the high-risk group was more sensitive to immunotherapy and certain chemotherapeutic agents. Anoikis-related prognostic signatures may provide a better understanding of the roles of ARGs and offer new perspectives for clinical prognosis and individualized treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Anoikis/genética , Carcinoma de Células Renais/genética , Calibragem , Neoplasias Renais/genética , Rim , Prognóstico , Microambiente Tumoral/genética
15.
Small ; 19(44): e2302197, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37403302

RESUMO

Synaptic devices that mimic biological synapses are considered as promising candidates for brain-inspired devices, offering the functionalities in neuromorphic computing. However, modulation of emerging optoelectronic synaptic devices has rarely been reported. Herein, a semiconductive ternary hybrid heterostructure is prepared with a D-D'-A configuration by introducing polyoxometalate (POM) as an additional electroactive donor (D') into a metalloviologen-based D-A framework. The obtained material features an unprecedented porous 8-connected bcu-net that accommodates nanoscale [α-SiW12 O40 ]4- counterions, displaying uncommon optoelectronic responses. Besides, the fabricated synaptic device based on this material can achieve dual-modulation of synaptic plasticity due to the synergetic effect of electron reservoir POM and photoinduced electron transfer. And it can successfully simulate learning and memory processes similar to those in biological systems. The result provides a facile and effective strategy to customize multi-modality artificial synapses in the field of crystal engineering, which opens a new direction for developing high-performance neuromorphic devices.

16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 52(1): 110-116, 2023 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37283124

RESUMO

OBJECTIVES: To investigate the risk factors of postoperative neuro-developmental abnormalities in neonates with critical congenital heart disease (CCHD). METHODS: Clinical data of 50 neonates with CCHD admitted in the Cardiac Intensive Care Unit, The Children's Hospital, Zhejiang University School of Medicine from November 2020 to December 2021 were retrospectively analyzed. Neurological assessment was performed with cranial ultrasonography, CT/MRI, video electroencephalogram and clinical symptoms before and after surgical treatment for all patients, and neurodevelopmental abnormalities were documented. Binary logistic stepwise regression was used to analyze risk factors of postoperative new-onset neurodysplasia in children with CCHD, and the predictive value of the risk factors on postoperative neurodevelopmental abnormalities were evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Neurodevelopmental abnormalities were detected in 22 cases (44.0%) and not detected in 28 cases (56.0%) before surgery. There were no significant differences in gender, birth weight, age at admission, gestational age, preoperative SpO2 level, prematurity, cyanotic congenital heart disease, and ventilator support between the two groups (all P>0.05). After surgery, there were 22 cases (44.0%) with new-onset neurological abnormalities and 28 cases (56.0%) without new-onset abnormalities. Multivariate logistic regression analysis showed that postoperative 24 h peak lactic acid (OR=1.537, 95%CI: 1.170-2.018, P<0.01) and postoperative length of ICU stay (OR=1.172, 95%CI:1.031-1.333, P<0.05) were independent risk factors for postoperative new-onset neurodevelopmental abnormalities. The area under ROC curve (AUC) of the postoperative 24 h peak lactic acid for predicting the new-onset neurological abnormalities after operation was 0.829, with cut-off value of 4.95 mmol/L. The diagnostic sensitivity and specificity were 90.0% and 64.3%, respectively. The AUC of postoperative length of ICU stay for predicting the new-onset neurological abnormalities after operation was 0.712, with cut-off value of 18.0 d. The diagnostic sensitivity and specificity were 50.0% and 96.4%, respectively. The AUC of the combination of the two indicators was 0.917, the diagnostic sensitivity and specificity were 95.5% and 64.3%, respectively. CONCLUSIONS: The incidence of neurodysplasia in neonatal CCHD is high, and new neurological abnormalities may occur after surgery. The postoperative 24 h peak lactic acid and postoperative length of ICU stay are risk factors for new-onset neurodysplasia after surgery. The combination of the two indicators has good predictive value for neurodevelopmental outcomes after surgery in CCHD infants.


Assuntos
Cardiopatias Congênitas , Recém-Nascido , Lactente , Criança , Humanos , Prognóstico , Estudos Retrospectivos , Curva ROC , Cardiopatias Congênitas/cirurgia , Fatores de Risco , Ácido Láctico
17.
Adv Mater ; 35(31): e2209799, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37276889

RESUMO

Photodynamic therapy (PDT) has achieved great success in cancer treatment. Despite its great promise, the efficacy of photodynamic immunotherapy can be limited by the hypoxia in solid tumors which is closely related to the abnormal tumor vasculature. These abnormal vasculatures are a hallmark of most solid tumors and facilitate immune evasion. Therefore, tumor vascular normalization is developed as a promising strategy to overcome tumor hypoxia, resulting in improved cancer therapy. Here, a NIR-II bio-degradable pseudo-conjugate polymer (PSP)-based photodynamic polymer is designed to deliver a vascular normalization agent, i.e., regorafenib (Reg) in nanoparticles (NP-PDT@Reg). NP-PDT@Reg under 808 nm laser irradiation (NP-PDT@Reg + L) can efficiently release Reg to improve the tumor hypoxia via vascular normalization, making more NP-PDT@Reg and oxygen enter the tumors. Moreover, NP-PDT@Reg + L can further result in generation of more reactive oxygen species (ROS) to eradicate tumor cells while inducing immunogenic cell death (ICD) to activate anti-tumor immune responses. In addition, Reg can reprogram TAM from a pro-tumor M2 phenotype to a tumor-killing M1 phenotype as well, thereby reversing the immunosuppressive tumor microenvironment. Taken together, the current study provides an innovative perspective on the development of novel nanomaterials to overcome the limitations in photodynamic immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Hipóxia Tumoral , Macrófagos Associados a Tumor , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Imunoterapia/métodos , Polímeros/farmacologia , Microambiente Tumoral
18.
PLoS One ; 18(4): e0284293, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37053153

RESUMO

Rapid economic development has led to increasingly serious air quality problems. Accurate air quality prediction can provide technical support for air pollution prevention and treatment. In this paper, we proposed a novel encoder-decoder model named as Enhanced Autoformer (EnAutoformer) to improve the air quality index (AQI) prediction. In this model, (a) The enhanced cross-correlation (ECC) is proposed for extracting the temporal dependencies in AQI time series; (b) Combining the ECC with the cross-stage feature fusion mechanism of CSPDenseNet, the core module CSP_ECC is proposed for improving the computational efficiency of the EnAutoformer. (c) The time series decomposition and dilated causal convolution added in the decoder module are exploited to extract the finer-grained features from the original AQI data and improve the performance of the proposed model for long-term prediction. The real-world air quality datasets collected from Lanzhou are used to validate the performance of our prediction model. The experimental results show that our EnAutoformer model can greatly improve the prediction accuracy compared to the baselines and can be used as a promising alternative for complex air quality prediction.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Desenvolvimento Econômico
19.
Adv Mater ; 35(24): e2301468, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37014930

RESUMO

Light-stimulated optoelectronic synaptic devices are fundamental compositions of the neuromorphic vision system. However, there are still huge challenges to achieving both bidirectional synaptic behaviors under light stimuli and high performance. Herein, a bilayer 2D molecular crystal (2DMC) p-n heterojunction is developed to achieve high-performance bidirectional synaptic behaviors. The 2DMC heterojunction-based field effect transistor (FET) devices exhibit typical ambipolar properties and remarkable responsivity (R) of 3.58×104 A W-1 under weak light as low as 0.008 mW cm-2 . Excitatory and inhibitory synaptic behaviors are successfully realized by the same light stimuli under different gate voltages. Moreover, a superior contrast ratio (CR) of 1.53×103 is demonstrated by the ultrathin and high-quality 2DMC heterojunction, which transcends previous optoelectronic synapses and enables application for the motion detection of the pendulum. Furthermore, a motion detection network based on the device is developed to detect and recognize classic motion vehicles in road traffic with an accuracy exceeding 90%. This work provides an effective strategy for developing high-contrast bidirectional optoelectronic synapses and shows great potential in the intelligent bionic device and future artificial vision.

20.
Food Chem Toxicol ; 176: 113756, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36997055

RESUMO

Aflatoxin G1 (AFG1), a member of the aflatoxin family with cytotoxic and carcinogenic properties, is one of the most common mycotoxins occurring in various agricultural products, animal feed, and human foods and drinks worldwide. Epithelial cells in the gastrointestinal tract are the first line of defense against ingested mycotoxins. However, the toxicity of AFG1 to gastric epithelial cells (GECs) remains unclear. In this study, we explored whether and how AFG1-induced gastric inflammation regulates cytochrome P450 to contribute to DNA damage in GECs. Oral administration of AFG1 induced gastric inflammation and DNA damage in mouse GECs associated with P450 2E1 (CYP2E1) upregulation. Treatment with the soluble TNF-α receptor sTNFR:Fc inhibited AFG1-induced gastric inflammation, and reversed CYP2E1 upregulation and DNA damage in mouse GECs. TNF-α-mediated inflammation plays an important role in AFG1-induced gastric cell damage. Using the human gastric cell line GES-1, AFG1 upregulated CYP2E1 through NF-κB, causing oxidative DNA damage in vitro. The cells were also treated with TNF-α and AFG1 to mimic AFG1-induced TNF-α-mediated inflammation. TNF-α activated the NF-κB/CYP2E1 pathway to promote AFG1 activation, which enhanced DNA cellular damage in vitro. In conclusion, AFG1 ingestion induces TNF-α-mediated gastric inflammation, which upregulates CYP2E1 to promote AFG1-induced DNA damage in GECs.


Assuntos
Aflatoxinas , Citocromo P-450 CYP2E1 , Camundongos , Humanos , Animais , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , NF-kappa B/metabolismo , Células Epiteliais/metabolismo , Aflatoxinas/toxicidade , Estresse Oxidativo , Inflamação/induzido quimicamente
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