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1.
J Colloid Interface Sci ; 672: 363-369, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38850863

RESUMO

HYPOTHESIS: Switchable microemulsions (MEs) are those capable of adaptively responding to the action of internal or external stimuli. For redox-switchable MEs to obtain high-efficiency phase separation and surfactant recycling, it may be one of the keys to adequately turn off the interfacial activity of surfactants and reduce the solubility of the closed surfactants in the oil phase. EXPERIMENTS: Monophasic MEs consisting 11-butylselanyl-undecyl sulfate sodium (C4SeC11SO4Na), n-butanol, n-octane, and water were fabricated using the pseudo-ternary phase diagram method. Their structural features and droplets size were characterized by conductivity, dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM), respectively. The redox response of MEs was studied using a combination of visual observations and DLS, cryo-TEM, nuclear magnetic resonance (NMR) and thin-layer tomography. The efficient recycling of C4SeC11SO4Na from a well-emulsified eluent is conceptually demonstrated. FINDINGS: The reversible transition between C4SeC11SO4Na and C4SeOC11SO4Na is achieved under the alternating action of H2O2 and N2H4, by which C4SeC11SO4Na-based monophasic MEs are able to efficiently demulsify and regenerate, respectively, regardless of their type. After H2O2-induced demulsification of the MEs, C4SeOC11SO4Na can be efficiently recycled with the water phase. We hope that such a redox-switching method may benefit some technological applications. For example, it offers exciting possibilities for simultaneous recycling C4SeC11SO4Na and removal of oil from a well-emulsified eluent. Around 97.1 ± 0.3 % of C4SeC11SO4Na could be recycled over five cycles with no apparent loss. After a simple and conventional treatment with anion-exchange resin and active carbon, the total organic carbon and chemical oxygen demand of the waste water were 17.4 ± 2.8 and 26.2 ± 1.4 mg/L, respectively.

2.
J Ethnopharmacol ; 333: 118442, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852640

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Jinmaitong (JMT) is a prescription of Traditional Chinese Medicine that is composed of 12 crude drugs. It has been used in the treatment of diabetic neuropathic pain (DNP) for more than 30 years. AIM OF STUDY: Microglia are thought to play an important role in neuropathic pain. This study aimed to evaluate the protective effect of JMT against DNP and to investigate the underlying mechanisms in which the microglia and JAK2/STAT3 signaling pathway were mainly involved. MATERIALS AND METHODS: The chemical composition of JMT was analyzed using liquid chromatography tandem mass spectrometry. The diabetes model was constructed using 11 to 12-week-old male Zucker diabetic fatty (ZDF) rat (fa/fa). The model rats were divided into 5 groups and were given JMT at three dosages (11.6, 23.2, and 46.4 g/kg, respectively, calculated as the crude drug materials), JAK inhibitor AG490 (positive drug, 10 µg/day), and placebo (deionized water), respectively, for eight weeks (n = 6). Meanwhile, Zucker lean controls (fa/+) were given a placebo (n = 6). Body weight was tested weekly and blood glucose was monitored every 2 weeks. The mechanical allodynia and heat hyperalgesia were assessed using mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests. After treatment, the microglia activation marker Iba-1, CD11B, CD68, neuroinflammatory mediators, and mediators of the JAK2/STAT3 signaling pathway were compared between different groups. The mRNA and protein levels of target genes were assessed by quantitative real-time PCR and Western Blot, respectively. RESULTS: We found that JMT significantly inhibited the overactivation of microglia in spinal cords, and suppressed neuroinflammation of DNP model rats, thereby ameliorating neurological dysfunction and injuries. Furthermore, these effects of JMT could be attributed to the inhibition of the JAK2/STAT3 signaling pathway. CONCLUSIONS: Our findings suggested that JMT effectively ameliorated DNP by modulating microglia activation via inhibition of the JAK2/STAT3 signaling pathway. The present study provided a basis for further research on the therapeutic strategies of DNP.

3.
Sensors (Basel) ; 24(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38732803

RESUMO

A two-stage decoupling model based on an artificial neural network with polynomial regression is proposed for the six-component force sensor load decoupling problem in the case of multidimensional mixed loading. The six-dimensional load categorization stage model constructed in the first stage combines 63 load category label sets with a deep BP neural network. The six-dimensional load regression stage model was constructed by combining polynomial regression with a BP neural network in the second stage. Meanwhile, the six-component force sensor with a fiber Bragg grating (FBG) sensor as the sensitive element was designed, and the elastomer simulation and calibration experimental dataset was established to realize the validation of the two-stage decoupling model. The results based on the simulation data show that the accuracy of the classification stage is 93.65%. The MAPE for the force channel in the regression stage is 6.29%, and 3.24% for the moment channel. The results based on experimental data show that the accuracy of the classification stage is 87.80%. The MAPE for the force channel in the regression phase is 5.63%, and 4.82% for the moment channel.

4.
ACS Pharmacol Transl Sci ; 7(5): 1386-1394, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38751617

RESUMO

Advanced metastatic colorectal cancer (mCRC) and the development of drug resistance to chemotherapy pose significant challenges in clinical settings. In previous studies, we have demonstrated the potent cytotoxic activity of (E)-3-(6-fluoro-1H-indol-3-yl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (FC116) and related 30 derivatives against mCRC by targeting microtubules. In this study, we aimed to evaluate the efficacy of the 31 compounds and explore the structure-activity relationship (SAR) against oxaliplatin-resistant mCRC. We found that most of the derivatives showed high sensitivity toward the oxaliplatin-resistant HCT-116/L cells. Particularly, FC116 exhibited a better GI50 value against the resistant mCRC cell line, HCT-116/L, compared to standard therapies. We also observed a safer therapeutic window for FC116 and a synergistic effect when it was used in combination with oxaliplatin. Mechanistically, FC116 induced the G2/M phase arrest by downregulating cyclin B1 expression through its interaction with microtubules in resistant colorectal cancer cells. Furthermore, in vivo experiments demonstrated that FC116 significantly suppressed tumor growth, achieving a 78% reduction at a dose of 3 mg/kg, which was superior to the 40% reduction achieved by oxaliplatin treatment. Overall, our findings suggest that the indole-chalcone compound FC116 represents a promising lead for chemotherapy in oxaliplatin-resistant mCRC.

5.
ACS Nano ; 18(17): 11217-11233, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38627234

RESUMO

Due to its intrinsic tumor-targeting attribute, limited immunogenicity, and cage architecture, ferritin emerges as a highly promising nanocarrier for targeted drug delivery. In the effort to develop ferritin cage-encapsulated cisplatin (CDDP) as a therapeutic agent, we found unexpectedly that the encapsulation led to inactivation of the drug. Guided by the structural information, we deciphered the interactions between ferritin cages and CDDP, and we proposed a potential mechanism responsible for attenuating the antitumor efficacy of CDDP encapsulated within the cage. Six platinum prodrugs were then designed to avoid the inactivation. The antitumor activities of these ferritin-platinum prodrug complexes were then evaluated in cells of esophageal squamous cell carcinoma (ESCC). Compared with free CDDP, the complexes were more effective in delivering and retaining platinum in the cells, leading to increased DNA damage and enhanced cytotoxic action. They also exhibited improved pharmacokinetics and stronger antitumor activities in mice bearing ESCC cell-derived xenografts as well as patient-derived xenografts. The successful encapsulation also illustrates the critical significance of comprehending the interactions between small molecular drugs and ferritin cages for the development of precision-engineered nanocarriers.


Assuntos
Antineoplásicos , Cisplatino , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferritinas , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Humanos , Ferritinas/química , Ferritinas/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Camundongos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Cisplatino/farmacologia , Cisplatino/química , Desenho de Fármacos , Platina/química , Platina/farmacologia , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sistemas de Liberação de Medicamentos
6.
Biomater Sci ; 12(8): 1965-1980, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38454904

RESUMO

Many studies suggest that tumor microbiome closely relates to the oncogenesis and anti-tumor responses in multiple cancer types (e.g., colorectal cancer (CRC), breast cancer, lung cancer and pancreatic cancer), thereby raising an emerging research area of bacteria-related tumor therapy. Nanomaterials have long been used for both cancer and bacterial infection treatment, holding great potential for bacteria-related tumor therapy. In this review, we summarized recent progress in nanomaterials for bacteria-related tumor therapy. We focus on the types and mechanisms of pathogenic bacteria in the development and promotion of cancers and emphasize how nanomaterials work. We also briefly discuss the design principles and challenges of nanomaterials for bacteria-related tumor therapy. We hope this review can provide some insights into this emerging and rapidly growing research area.


Assuntos
Neoplasias Pulmonares , Nanoestruturas , Neoplasias Pancreáticas , Humanos , Bactérias , Transformação Celular Neoplásica , Nanoestruturas/uso terapêutico
7.
Food Chem X ; 21: 101241, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38434691

RESUMO

The effects of perilla seed oil high internal phase emulsions stabilized by pea protein (PP-PSO HIPEs) on the gel properties and conformation of myofibrillar protein (MP) gels were investigated. The results showed that the PP-PSO HIPEs with 4.0 % (w/v) PP formed stable HIPEs with low droplet size and good viscoelasticity. The addition of PP-PSO HIPEs (5.0 % - 15.0 %) could significantly improve the MP gel properties (P < 0.05), while the addition of 10.0 % PP-PSO HIPEs showed the highest gel strength and water holding capacity. Otherwise, the MP gels with 10.0 % PP-PSO HIPEs showed higher proportions of immobile water (PT22) and lower proportion of free water (PT23), and the Raman spectra suggested that the content of α-helix decreased, while the content of ß-sheet increased (P < 0.05), thus facilitating the formation of better gel properties. Therefore, the addition of PP-PSO HIPEs is a potential alternative for developing fat-reduced meat products.

8.
Front Pharmacol ; 15: 1359954, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495103

RESUMO

Introduction: The purpose of this study was to identify the chemical components of Massa Medicata Fermentata (MMF) in different fermentation methods, analyze its regulatory effects on gastrointestinal propulsion and intestinal flora in mice with food accumulation, and further explore its mechanism of action in the treatment of dyspepsia. Methods: The chemical compositions of three kinds of MMF were identified using the UPLC-Q- Exactive Orbitrap mass spectrometer. A model of spleen deficiency and food accumulation in mice was established. The gastric emptying rate and intestinal propulsion rate were calculated, serum gastrin concentration and cholinesterase activity were measured, and 16S rRNA microbial detection was performed in different groups of mouse feces. Results: The results showed that a total of 95 chemical components were identified from the three MMF extracts, 62 of which were the same, but there were differences in flavonoids and their glycosides, organic acids, and esters. MMF, PFMMF, and commercial MMF could all significantly improve the gastric emptying rate, intestinal propulsion rate, and GAS concentration in the serum of model mice; PFMMF has a better effect, while there was no significant difference in cholinesterase activity among the groups (p > 0.05). The 16S rRNA sequencing results showed that the MMF and PFMMF could increase the content of beneficial bacteria Bacteroidetes and decrease the pathogenic bacteria Verrucomicrobia in the intestines of model mice, while the commercial MMF could not. Discussion: Studies suggest that MMF has a variety of possible mechanisms for improving food accumulation and treating gastrointestinal dyspepsia, which provides reference value for the quality evaluation and clinical application of MMF.

9.
World J Clin Cases ; 12(3): 560-564, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38322470

RESUMO

BACKGROUND: We report a low-birth-weight child (1.8 kg) with neonatal type III congenital esophageal atresia (CEA) combined with symptomatic patent ductus arteriosus (PDA). After comprehensive evaluation, esophageal anastomosis was performed on postnatal day 11 after excluding surgical contraindications, and arterial catheter ligation was performed at the same time. Concurrent surgery for CEA combined with PDA has not been clearly reported in the literature. CASE SUMMARY: We report a 6-day-old female child with type III CEA and PDA. The patient presented with foam at the mouth after birth, cough and shortness of breath after feeding. At another hospital, she was considered to have neonatal pneumonia, neonatal jaundice and congenital heart disease and transferred to our hospital. After iodine oil radiography of the esophagus and echocardiography we confirmed diagnosis of CEA and PDA. The diameter of the PDA was 8 mm, with obvious left to right shunting. We performed right rear extrapleural orificium fistula ligation and esophageal anastomosis, and ligation of PDA via left axilla straight incision after 5 d of hospitalization. The operations were successful, and the incision healed after 12 d, and the patient was discharged. We re-examined the patient 1 mo after surgery. She did not vomit when she ate rice flour. Esophageal angiography showed no stricture of the anastomotic stoma. The patient weighed 3.2 kg. CONCLUSION: For CEA patients with multiple risk factors, comprehensive, timely and accurate diagnosis and evaluation, and early treatment may improve prognosis.

10.
J Affect Disord ; 350: 831-837, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38242215

RESUMO

BACKGROUND: The objective of this study was to provide a comprehensive analysis of the spatial distribution and temporal trends in the age-standardized incidence rates (ASIRs) of depression in adolescents aged 10-24 worldwide. METHODS: Data from the Global Burden of Disease Study (GBD) 2019 were analyzed, adopting Sawyer's broad definition of adolescence encompassing ages 10 to 24. Estimated annual percentage changes (EAPCs) were used to assess temporal trends. RESULTS: Globally, from 1990 to 2019, there was a decrease in the ASIR of depression in adolescents (EAPC = -0.23). Notably, this decrease was more pronounced in female adolescents compared to their male counterparts (EAPC = -0.12 and - 0.29, respectively). Conversely, high Sociodemographic Index (SDI) regions experienced a significant increase in the ASIR of depression among adolescents (EAPC = 0.87). Furthermore, it is worth mentioning that individuals aged 20-24 exhibited the highest incidence rate for depression followed by those aged 15-19 and then those aged 10-14. The largest increases in the ASIRs of depression occurred in High-income North America (EAPC = 1.19) and Malaysia (EAPC = 2.4), respectively. LIMITATIONS: Mathematical models were used to reconstruct and adjust data of different qualities, which might have introduced bias. CONCLUSIONS: The global burden of disease for depression among adolescents aged 10-24 years declined from 1990 to 2019. Special attention must be paid to older adolescents and areas with higher SDIs.


Assuntos
Depressão , Produtos Finais de Glicação Avançada , Humanos , Adolescente , Feminino , Masculino , Depressão/epidemiologia , Incidência , Renda , Malásia , Saúde Global , Anos de Vida Ajustados por Qualidade de Vida
11.
PeerJ ; 11: e16600, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089911

RESUMO

DNA 5-methylcytosine (5mC) is widely present in multicellular eukaryotes, which plays important roles in various developmental and physiological processes and a wide range of human diseases. Thus, it is essential to accurately detect the 5mC sites. Although current sequencing technologies can map genome-wide 5mC sites, these experimental methods are both costly and time-consuming. To achieve a fast and accurate prediction of 5mC sites, we propose a new computational approach, BERT-5mC. First, we pre-trained a domain-specific BERT (bidirectional encoder representations from transformers) model by using human promoter sequences as language corpus. BERT is a deep two-way language representation model based on Transformer. Second, we fine-tuned the domain-specific BERT model based on the 5mC training dataset to build the model. The cross-validation results show that our model achieves an AUROC of 0.966 which is higher than other state-of-the-art methods such as iPromoter-5mC, 5mC_Pred, and BiLSTM-5mC. Furthermore, our model was evaluated on the independent test set, which shows that our model achieves an AUROC of 0.966 that is also higher than other state-of-the-art methods. Moreover, we analyzed the attention weights generated by BERT to identify a number of nucleotide distributions that are closely associated with 5mC modifications. To facilitate the use of our model, we built a webserver which can be freely accessed at: http://5mc-pred.zhulab.org.cn.


Assuntos
5-Metilcitosina , DNA , Humanos , DNA/genética , Fontes de Energia Elétrica , Eucariotos , Idioma
12.
Sci Data ; 10(1): 890, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086806

RESUMO

U-Net, a deep-learning convolutional neural network, is used to downscale coarse meteorological data. Based on 19 models from the Coupled Model Intercomparison Project Phase 6 and the Multi-Source Weather (MSWX) dataset, bias correction and UNet downscaling approaches are used to develop high resolution dataset over the East Asian region, referred to as Climate Change for East Asia with Bias corrected UNet Dataset (CLIMEA-BCUD). CLIMEA-BCUD provides nine meteorological variables including 2-m air temperature, 2-m daily maximum air temperature, 2-m daily minimum air temperature, precipitation, 10-m wind speed, 2-m relative humidity, 2-m specific humidity, downward shortwave radiation and downward longwave radiation with 0.1° horizontal resolution at daily intervals over the historical period of 1950-2014 and three future scenarios (SSP1-2.6, SSP2-4.5 and SSP5-8.5) of 2015-2100. Validation against MSWX indicates that CLIMEA-BCUD shows reasonable performance in terms of climatology, and it is capable of simulating seasonal cycles and future changes well. It is suggested that CLIMEA-BCUD can promote the application of deep learning in climate research in the areas of climate change, hydrology, etc.

13.
Phys Med Biol ; 68(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37918023

RESUMO

Objective. It was a great challenge to train an excellent and generalized model on an ultra-small data set composed of multi-orientation cardiac cine magnetic resonance imaging (MRI) images. We try to develop a 3D deep learning method based on an ultra-small training data set from muti-orientation cine MRI images and assess its performance of automated biventricular structure segmentation and function assessment in multivendor.Approach. We completed the training and testing of our deep learning networks using only heart datasets of 150 cases (90 cases for training and 60 cases for testing). This datasets were obtained from three different MRI vendors and each subject included two phases of the cardiac cycle and three cine sequences. A 3D deep learning algorithm combining Transformers and U-Net was trained. The performance of the segmentation was evaluated using the Dice metric and Hausdorff distance (HD). Based on this, the manual and automatic results of cardiac function parameters were compared with Pearson correlation, intraclass correlation coefficient (ICC) and Bland-Altman analysis in multivendor.Main results. The results show that the average Dice of 0.92, 0.92, 0.94 and HD95 of 2.50, 1.36, 1.37 for three sequences. The automatic and manual results of seven parameters were excellently correlated with the lowestr2 value of 0.824 and the highest of 0.983. The ICC (0.908-0.989,P< 0.001) showed that the results were highly consistent. Bland-Altman with a 95% limit of agreement showed there was no significant difference except for the difference in RVESV (P= 0.005) and LVM (P< 0.001).Significance. The model had high accuracy in segmentation and excellent correlation and consistency in function assessment. It provides a fast and effective method for studying cardiac MRI and heart disease.


Assuntos
Imagem Cinética por Ressonância Magnética , Redes Neurais de Computação , Imagem Cinética por Ressonância Magnética/métodos , Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Algoritmos
14.
Nat Commun ; 14(1): 7041, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923715

RESUMO

Waveguide metatronics, known as an advanced platform of metamaterial-inspired circuits, provides a promising paradigm for millimeter-wave and terahertz integrated circuits in future fifth/sixth generation (5/6G) communication systems. By exploiting the structural dispersion properties of waveguides, a lumped type of waveguide integrated elements and circuits could be developed in deep subwavelength scales with intrinsic low loss and low crosstalk. In this study, we focus on constructing negative capacitors and inductors for waveguide metatronics, effectively expanding the operating frequency range of waveguide integrated circuits. The incorporation of negative elements enables wideband impedance matching in waveguide, which have been both theoretically explored and experimentally validated within the waveguide metatronics paradigm. Furthermore, we have demonstrated that the negative elements can also be realized in the optical domain through the utilization of a silicon waveguide with photonic crystal cladding, indicating the feasibility and universality of wideband waveguide metatronics. The negative lumped elements could boost the progress of the waveguide metatronic technique, achieving superior performance on the conventional lumped circuits within waveguides that solely rely on positive elements.

15.
Polymers (Basel) ; 15(22)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38006096

RESUMO

Isosorbide can be used as a third monomer in the synthesis of aliphatic polyesters, and its V-shaped bridging ring structure can effectively improve the rigidity of the copolyester molecular chain. In this work, a series of degradable polyester materials were prepared by modifying polybutylene succinate and using isosorbide as the third monomer. The degradation tests in this paper were implemented through the hydrolysis of copolyesters in distilled water, degradation in natural water and degradation tests in simulated natural environments. The results showed that PBS and its copolyesters can degrade under natural conditions, and the introduction of isosorbide can accelerate the degradation of copolyesters, which could effectively reduce pollutants in nature.

16.
Hum Reprod ; 38(Supplement_2): ii3-ii13, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982416

RESUMO

Recent developments in molecular biological technologies and genetic diagnostic methods, accompanying with updates of relevant terminologies, have enabled the improvements of new strategies of preimplantation genetic testing for monogenic (single gene) disorders (PGT-M) to prevent the transmission of inherited diseases. However, there has been much in the way of published consensus on PGT-M. To properly regulate the application of PGT-M, Chinese experts in reproductive medicine and genetics have jointly developed this consensus statement. The consensus includes indications for patient selection, genetic and reproductive counseling, informed consent, diagnostic strategies, report generation, interpretation of results and patient follow-ups. This consensus statement serves to assist in establishment of evidence-based clinical and laboratory practices for PGT-M.


Assuntos
Diagnóstico Pré-Implantação , Feminino , Humanos , Gravidez , Aneuploidia , Aconselhamento , Testes Genéticos/métodos , Diagnóstico Pré-Implantação/métodos , China
17.
Brain Res Bull ; 204: 110792, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37858681

RESUMO

BACKGROUND: ANO1 is closely correlated with the activation of EGFR and CaMKII, while EGFR and CaMKII show low activation in amyotrophic lateral sclerosis (ALS) models. Therefore, we designed experiments to verify that ANO1 may play a protective role on motor neurons in ALS by activating EGFR and CaMKII. METHODS: The expression changes of ANO1, EGFR, CaMKII, pEGFR, and pCaMKII, cell survival status, and apoptosis were studied by western blot, real-time quantitative PCR, immunofluorescence, immunohistochemistry, CCK-8, and flow cytometry. The role of ANO1 in the ALS model by activating EGFR and CaMKII was studied by applying corresponding activators, inhibitors, gene silencing, and overexpression. RESULTS: In hSOD1G93A transgenic animals and cell lines, low expression of ANO1 and low activation of EGFR and CaMKII were identified. ANO1 expression decreased gradually with the progression of ALS. Overexpression of ANO1 in the hSOD1G93A cell line and primary neurons of hSOD1G93A transgenic mice increased cell viability and decreased cell apoptosis. After the application of ANO1 inhibitor CaCC-inhA01 in hSOD1G93A cell line and primary neurons of hSOD1G93A transgenic mice, EGFR activator EGF and CaMKII activator Carbachol, increased cell viability and reduced cell apoptosis. After ANO1 was overexpressed in the hSOD1G93A cell line and primary neurons of hSOD1G93A transgenic mice, EGFR inhibitor AEE788 and CaMKII inhibitor KN93 decreased cell viability and increased cell apoptosis. CONCLUSIONS: Our results suggest that ANO1 plays an important role in the survival of ALS motor neurons. ANO1 can increase cell activity and reduce apoptosis by activating EGFR and CaMKII signals.


Assuntos
Esclerose Lateral Amiotrófica , Animais , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , Anoctamina-1 , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Canais de Cloreto , Modelos Animais de Doenças , Receptores ErbB/metabolismo , Camundongos Transgênicos , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/metabolismo
18.
Comput Biol Chem ; 107: 107952, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37643501

RESUMO

Predicting protein stability change upon variation through a computational approach is a valuable tool to unveil the mechanisms of mutation-induced drug failure and develop immunotherapy strategies. Some previous machine learning-based techniques exhibit anti-symmetric bias toward destabilizing situations, whereas others struggle with generalization to unseen examples. To address these issues, we propose a gated graph neural network-based approach to predict changes in protein stability upon mutation. The model uses message passing to encode the links between the molecular structure and property after eliminating the non-mutant structure and creating input feature vectors. While doing so, it also incorporates the coordinates of the raw atoms to provide spatial insights into the chemical systems. We test the model on the Ssym, Myoglobin, Broom, and p53 datasets to demonstrate the generalization performance. Compared to existing approaches, our proposed method achieves improved linearity with symmetry in less time. The code for this study is available at: https://github.com/HongzhouTang/Pros-GNN.


Assuntos
Imunoterapia , Aprendizado de Máquina , Estabilidade Proteica , Mutação , Redes Neurais de Computação
19.
Heart Vessels ; 38(12): 1459-1467, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37650926

RESUMO

Myocardium baseline impedance (BI) is an important factor in ablation effectiveness. This study examined the performance of low-power and long-duration (LPLD), high-power and short-duration (HPSD) ablation at different BIs by computer simulation. A 3D model of the ablation region was constructed for simulation, and in vitro experiments were performed to validate the simulation. Three ablation power and duration configurations of 30 W/30 s, 50 W/10 s, and 90 W/5 s were used for simulation with BI values of 90, 100, 110, 120, 130, and 140 Ω. Roll-off time and ablation volume were measured to evaluate ablation results. The simulation is consistent with the in vitro experiments. When BI is changed from 90 [Formula: see text] to 140 [Formula: see text], the lesion volume over 50 °C with BI of 140 [Formula: see text] was reduced by 6.3%, 6.7%, and 7.3% for 30 W/30 s, 50 W/10 s, and 90 W/5 s configurations, respectively, and the lesion volume over 100 °C was reduced by 62.8%, 49.7%, and 22.5% under 30 W/30 s, 50 W/10 s, and 90 W/5 s, respectively. Simulation results revealed that HPSD (vHPSD) and LPLD ablation were more affected by changes in BI in the lesion volumes over 50 °C and 100 °C, respectively, and demonstrated that resistive and conductive heating were the main heating effects in HPSD (vHPSD) and LPLD, respectively.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Simulação por Computador , Impedância Elétrica , Ablação por Cateter/métodos , Miocárdio/patologia , Fatores de Tempo , Fibrilação Atrial/cirurgia , Veias Pulmonares/cirurgia , Resultado do Tratamento
20.
Arch Med Sci ; 19(4): 930-940, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560733

RESUMO

Introduction: The aim of this study was to understand the global incidence and disability-adjusted life years (DALY) of oral disorders by age, gender, region, and Sociodemographic Index (SDI) from 1990 to 2019. Material and methods: The estimated annual percentage change (EAPC) and 95% confidence intervals (CIs) were used to assess the trends in age-standardized incidence and DALY rates from 1990 to 2019. Results: The global age-standardized incidence rate (EAPC = 0.01) of oral disorders increased slightly from 1990 to 2019. From 1990 to 2019, the age-standardized DALY rate decreased in high-SDI (EAPC = -0.43) and high-middle-SDI (EAPC = -0.14) regions, but it showed increasing trends in low-SDI (EAPC = 0.22), low-middle-SDI (EAPC = 0.36), and middle-SDI (EAPC = 0.17) regions. The EAPC in the age-standardized DALY rate was negatively correlated with the regional SDI value (ρ = -0.402, p = 0.001). From 1990 to 2019, the region with the largest increase in age-standardized DALY rate was South Asia (EAPC = 0.67), while the country with the greatest increase in age-standardized DALY rate was India (EAPC = 0.82). Conclusions: From 1990 to 2019, the global age-standardized incidence rate of oral disorders showed a slight increasing trend. It is necessary to control the increase in DALY and the disease burden associated with oral disorders in low-, low-middle-, and middle-SDI regions, such as South Asia, particularly in India.

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