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1.
Brain Res Bull ; 211: 110950, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631651

RESUMO

The aim of this study was to investigate the expression and function of the transient receptor potential vanilloid 1 (TRPV1) in glioma. We found that the expression of TRPV1 mRNA and protein were upregulated in glioma compared with normal brain by qPCR and western blot analysis. In order to investigate the function of TRPV1 in glioma, short hairpin RNA (shRNA) and the inhibitor of TRPV1 were used. In vitro, the activation of TRPV1 induced cell apoptosis with decreased migration capability and inhibited proliferation, which was abolished upon TRPV1 pharmacological inhibition and silencing. Mechanistically, TRPV1 modulated glioma proliferation through the protein kinase B (Akt) signaling pathway. More importantly, in immunodeficient (NOD-SCID) mouse xenograft models, tumor size was significantly increased when TRPV1 expression was disrupted by a shRNA knockdown approach in vivo. Altogether, our findings indicate that TRPV1 negatively controls glioma cell proliferation in an Akt-dependent manner, which suggests that targeting TRPV1 may be a potential therapeutic strategy for glioma.

2.
Am J Clin Nutr ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608754

RESUMO

BACKGROUND: Evidence regarding the relationships of serum 25-hydroxyvitamin D (25[OH]D) with cardiovascular diseases (CVD) and mortality among patients with chronic kidney disease (CKD) is limited and inconsistent. OBJECTIVE: This study aimed to investigate the associations between serum 25(OH)D and CVD incidence and mortality among patients with CKD. METHODS: This prospective study included 21,507 participants with CKD and free of CVD in the UK Biobank. Incidences of total and subtypes of CVD and mortality were ascertained via electronic health records. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) for CVD incidence and mortality. RESULTS: The median serum 25(OH)D concentration was 44.0 nmol/L (interquartile range: 30.1, 60.6 nmol/L). After multivariable adjustment, compared with CKD patients with serum 25(OH)D <25 nmol/L, those with serum 25(OH)D ≥75 nmol/L had HRs (95% CIs) of 0.80 (0.71, 0.90) for total CVD incidence, 0.82 (0.69, 0.97) for ischemic heart disease, 0.56 (0.41, 0.77) for stroke, 0.64 (0.46, 0.88) for myocardial infarction, 0.62 (0.49, 0.80) for heart failure, 0.60 (0.43, 0.85) for CVD mortality, and 0.62 (0.52, 0.74) for all-cause mortality. In addition, these associations were not modified by VDR polymorphisms, with no significant interaction was detected. CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risks of total and subtypes of CVD incidence and mortality among individuals with CKD. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of CVD and mortality in patients with CKD.

3.
J Clin Pharmacol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654529

RESUMO

Voriconazole is the first-line treatment for invasive aspergillosis. Its pharmacokinetics exhibit considerable inter- and intra-individual variability. The purpose of this study was to investigate the effects of CYP2C19, CYP2C9, CYP3A4, and FMO3 genetic polymorphisms and sex on the pharmacokinetics of voriconazole in healthy Chinese adults receiving single-dose and multiple-dose voriconazole, to provide a reference for its clinical individualized treatment. A total of 123 healthy adults were enrolled in the study, with 108 individuals and 15 individuals in the single-dose and multiple-dose doses, respectively. Plasma voriconazole concentrations were measured using a validated LC-MS/MS method, and pharmacokinetics parameters were calculated using the non-compartmental method with WinNonlin 8.2. CYP2C19, CYP2C9, CYP3A4, and FMO3 single-nucleotide polymorphisms were sequenced using the Illumina Hiseq X-Ten platform. The results suggested that CYP2C19 genetic polymorphisms significantly affected the pharmacokinetics of voriconazole at single doses of 4, 6, and 8 mg/kg and multiple doses of voriconazole. CYP3A4 rs2242480 had a significant effect on AUC0-∞ (area under the plasma concentration-time curve from time 0 to infinity) and MRT (mean residence time) of voriconazole at a single dose of 4 mg/kg in CYP2C19 extensive metabolizer. Regardless of the CYP2C19 genotype, CYP2C9 rs1057910 and FMO3 rs2266780 were not associated with the pharmacokinetics of voriconazole at three single-dose levels or multiple doses. No significant differences in most voriconazole pharmacokinetics parameters were noted between male and female participants after single and multiple dosing. For patients receiving voriconazole treatment, CYP2C19 genetic polymorphisms should be genotyped for its precision administration. In contrast, based on our study of healthy Chinese adults, it seems unnecessary to consider the effects of CYP2C9, CYP3A4, and FMO3 genetic polymorphisms on voriconazole pharmacokinetics.

4.
Front Endocrinol (Lausanne) ; 15: 1287930, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577572

RESUMO

Objective: To evaluate the role of foot muscle amide proton transfer weighted (APTw) contrast and tissue rest perfusion in quantifying diabetic foot (DF) infection and its correlation with blood parameters. Materials and methods: With approval from an ethical review board, this study included 40 diabetes mellitus (DM) patients with DF and 31 DM patients without DF or other lower extremity arterial disease. All subjects underwent MRI, which included foot sagittal APTw and coronal arterial spin labeling (ASL) imaging. The normalized MTRasym (3.5 ppm) and the ratio of blood flow (rBF) in rest status of the affected side lesions to the non-affected contralateral side were determined. The inter-group differences of these variables were evaluated. Furthermore, the association between normalized MTRasym (3.5 ppm), rBF, and blood parameters [fasting blood glucose (FBG), glycosylated hemoglobin content, C-reactive protein, neutrophil percentage, and white blood cell count] was explored. Using an ROC curve, the diagnostic capacity of normalized MTRasym (3.5 ppm), BF, and blood biochemical markers in differentiating with or without DF in DM was assessed. Results: In the DF group, MTRasym (3.5 ppm) and BF in lesion and normalized MTRasym (3.5 ppm) were higher than those in the control group (p < 0.05). In addition, correlations were identified between normalized MTRasym (3.5 ppm) and blood parameters, such as C-reactive protein, glycosylated hemoglobin content, FBG, neutrophil ratio, and white blood cell (p < 0.001). Meanwhile, association between BF in lesion and blood parameters, such as C-reactive protein, neutrophil percentage, and FBG (p < 0.01). AUC of normalized MTRasym (3.5 ppm) in identifying with/without DF in patients with DM is 0.986 (95% CI, 0.918-1.00) with the sensitivity of 97.22% and the specificity of 100%. Conclusion: Normalized MTRasym (3.5 ppm) and the BF in lesion may be treated as a safer and more convenient new indicator to evaluate the tissue infection without using a contrast agent, which may be useful in monitoring and preoperatively assessing DF patients with renal insufficiency.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Prótons , Pé Diabético/diagnóstico por imagem , Amidas/química , Proteína C-Reativa , Estudos de Casos e Controles , Hemoglobinas Glicadas , Imageamento por Ressonância Magnética/métodos
5.
Neurosurg Rev ; 47(1): 109, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456944

RESUMO

OBJECTIVE: To develop a clinical-radiomics nomogram based on clinical information and radiomics features to predict the prognosis of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia (TN). METHODS: The retrospective study involved clinical data from 149 TN patients undergoing PBC at Zhongnan Hospital, Wuhan University from January 2018 to January 2022. The free open-source software 3D Slicer was used to extract all radiomic features from the intraoperative X-ray balloon region. The relationship between clinical information and TN prognosis was analyzed by univariate logistic analysis and multivariate logistic analysis. Using R software, the optimal radiomics features were selected using the least absolute shrinkage and selection operator (Lasso) algorithm. A prediction model was constructed based on the clinical information and radiomic features, and a nomogram was visualized. The performance of the clinical radiomics nomogram in predicting the prognosis of PBC in TN treatment was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 149 patients were eventually included. The clinical factors influencing the prognosis of TN in univariate analysis were compression severity score and TN type. The lasso algorithm Max-Relevance and Min-Redundancy(mRMR) was used to select two predictors from 13 morphology-related radiomics features, including elongation and surface-volume ratio. A total of 4 predictors were used to construct a prediction model and nomogram. The AUC was 0.886(95% confidence interval (CI), 0.75 to 0.96), indicating that the model's good predictive ability. DCA demonstrated the nomogram's high clinical applicability. CONCLUSION: Clinical-radiomics nomogram constructed by combining clinical information and morphology-related radiomics features have good potential in predicting the prognosis of TN for PBC treatment. However, this needs to be further studied and validated in several independent external patient populations.


Assuntos
Nomogramas , Neuralgia do Trigêmeo , Humanos , 60570 , Estudos Retrospectivos , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/cirurgia , Prognóstico
6.
Curr Microbiol ; 81(5): 117, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492090

RESUMO

Atrazine is an important herbicide that has been widely used for weed control in recent decades. However, with the extensive use of atrazine, its residue seriously pollutes the environment. Therefore, the microbial degradation and detoxification of atrazine have received extensive attention. To date, the aerobic degradation pathway of atrazine has been well studied; however, little is known about its anaerobic degradation in the environment. In this study, an anaerobic microbial consortium capable of efficiently degrading atrazine was enriched from soil collected from an herbicide-manufacturing plant. Six metabolites including hydroxyatrazine, deethylatrazine, N-isopropylammelide, deisopropylatrazine, cyanuric acid, and the novel metabolite 4-ethylamino-6-isopropylamino-1,3,5-triazine (EIPAT) were identified, and two putative anaerobic degradation pathways of atrazine were proposed: a hydrolytic dechlorination pathway is similar to that seen in aerobic degradation, and a novel pathway initiated by reductive dechlorination. During enrichment, Denitratisoma, Thiobacillus, Rhodocyclaceae_unclassified, Azospirillum, and Anaerolinea abundances significantly increased, dominating the enriched consortium, indicating that they may be involved in atrazine degradation. These findings provide valuable evidence for elucidating the anaerobic catabolism of atrazine and facilitating anaerobic remediation of residual atrazine pollution.


Assuntos
Atrazina , Herbicidas , Poluentes do Solo , Atrazina/análise , Atrazina/química , Atrazina/metabolismo , Herbicidas/metabolismo , Solo/química , Anaerobiose , Consórcios Microbianos , Biodegradação Ambiental , Microbiologia do Solo , Poluentes do Solo/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-38546460

RESUMO

A Gram-stain-negative bacterium, designated as R-40T, was isolated from sediment of the Mulong river in Mianyang city, Sichuan province, PR China. The cells of strain R-40T were aerobic non-motile and formed translucent white colonies on R2A agar. Growth occurred at 15-37 °C (optimum 30 °C), pH 5.0-9.0 (optimum 7.0) and salinities of 0-3.0 % (w/v, optimum 0 %). R-40T showed 95.2-96.6 % 16S rRNA gene sequence similarities with the type strains of species of the genera Oxalicibacterium, Herminiimonas, Lacisediminimonas, Paucimonas, Herbaspirillum and Noviherbaspirillum in the family Oxalobacteraceae. The results of phylogenetic analysis based on genome sequences indicated that the strain was clustered with type strains of species of the genera Oxalicibacterium and Herminiimonas in the family Oxalobacteraceae but formed a distinct lineage. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH) and average amino acid identity (AAI) values between R-40T and type strains of species of the genera Oxalicibacterium, Herminiimonas, Lacisediminimonas, Paucimonas, Herbaspirillum and Noviherbaspirillum ranged from 69.3 to 74.1 %, from 18.2 to 21.4 % and from 60.1 to 67.4 %, respectively. The major cellular fatty acids were C16 : 0, C17 : 0 cyclo and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The major quinone was ubiquinone-8 (Q-8). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phospholipid and small amounts of glycophospholipids. The genome size of R-40T was 5.1 Mbp with 54.0 % DNA G+C content. On the basis of the evidence presented in this study, strain R-40T represents a novel species of a novel genus in the family Oxalobacteraceae, for which the name Keguizhuia sedimenti gen. nov., sp. nov. (type strain R-40T=MCCC 1K08818T=KCTC 8137T) is proposed.


Assuntos
Compostos Azo , Burkholderiaceae , Herbaspirillum , Oxalobacteraceae , Filogenia , RNA Ribossômico 16S/genética , Rios , Composição de Bases , Ácidos Graxos/química , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Oxalobacteraceae/genética
8.
Sensors (Basel) ; 24(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38339585

RESUMO

With the development of the integration and miniaturization of sensing devices, the concept of self-sensing devices has been proposed. A motion state is self-sensed via the structure or integration of an actuator in the construction of a sensing unit. This device is then used to capture the perception and measurement of states such as position, displacement, and speed. A triboelectric nanogenerator converts mechanical energy into electrical energy through the coupling effect of contact generation and electrostatic induction, which represents one of the reliable ways through which to realize integrated sensing. In this world, the power generation technology of the TENG is applied to a sensing device. The sensing characteristics of a grid-like TENG are designed and analyzed in freestanding triboelectric mode. Firstly, a relation model of displacement, velocity, voltage, and charge is established. The charge-transfer increment and current amounts are linearly related to the velocity. The open-circuit voltage has a positive relationship with the displacement. The maximum open-circuit voltage and the maximum charge transfer are fixed values, and they are only related to the inherent parameters of a triboelectric nanogenerator. Next, the sensor model is constructed using COMSOL Multiphysics 6.0. The simulation results show that the relationships between output voltage and charge transfer, as well as those between the increments of charge transfer, velocity, and displacement, are consistent with the results derived from the formula. Finally, a performance test of the designed sensor is carried out, and the results are consistent with the theoretical deduction and simulation. After analysis and processing of the output electrical signal by the host computer, it can feedback the frequency and speed value of the measured object. In addition, the output signal is stable, and there is no large fluctuation or attenuation during the 521-s vibration test. Because the working unit of the sensor is thin filmed, it is small in size, easy to integrate, and has no external power supply; moreover, it can be integrated into a device to realize the self-sensing of a motion state.

9.
Chem Biol Interact ; 387: 110811, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37993078

RESUMO

Ciprofol is a novel intravenous anesthetic agent. Its major glucuronide metabolite, M4, is found in plasma and urine. However, the specific isoforms of UDP-glucuronosyltransferases (UGTs) that metabolize ciprofol to M4 remain unknown. This study systematically characterized UGTs that contribute to the formation of M4 using human liver microsomes (HLM), human intestinal microsomes (HIM), and human recombinant UGTs. The inhibitory potential of ciprofol and M4 against major human UGTs and cytochrome P450 enzymes (P450s) was also explored. In vitro-in vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic (PBPK) simulations were performed to predict potential in vivo drug-drug interactions (DDIs) caused by ciprofol. Glucuronidation of ciprofol followed Michaelis-Menten kinetics in both HLM and HIM with apparent Km values of 345 and 412 µM, Vmax values of 2214 and 444 nmol min-1·mg protein-1, respectively. The in vitro intrinsic clearances (CLint = Vmax/Km) for ciprofol glucuronidation by HLM and HIM were 6.4 and 1.1 µL min-1·mg protein-1, respectively. Human recombinant UGT studies revealed that UGT1A9 is the predominant isoform mediating M4 formation, followed by UGT1A7, with UGT1A8 playing a minor role. Ciprofol competitively inhibited CYP1A2 (Ki = 12 µM) and CYP2B6 (Ki = 4.7 µM), and noncompetitively inhibited CYP2C19 (Ki = 29 µM). No time-dependent inhibition by ciprofol was noted for CYP1A2, CYP2B6, or CYP2C19. In contrast, M4 showed limited or no inhibitory effects against selected P450s. Neither ciprofol nor M4 inhibited UGTs significantly. Initial IVIVE suggested potential ciprofol-mediated inhibition of CYP1A2, CYP2B6, and CYP2C19 inhibition in vivo. However, PBPK simulations showed no significant effect on phenacetin, bupropion, and S-mephenytoin exposure or peak plasma concentration. Our findings are pertinent for future DDI studies of ciprofol as either a perpetrator or victim drug.


Assuntos
Citocromo P-450 CYP1A2 , Microssomos Hepáticos , Humanos , Citocromo P-450 CYP2B6/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2C19/metabolismo , Microssomos Hepáticos/metabolismo , Glucuronosiltransferase/metabolismo , Interações Medicamentosas , Cinética
10.
Nanotechnology ; 35(1)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37757767

RESUMO

In this paper, we propose a dual-operating mode metasurface based on graphene and vanadium dioxide (VO2), which can switch operating modes by changing the temperature. At room temperature (25 °C), the metasurface can generates a polarization-insensitive electromagnetically induced transparency (EIT)-like effect that can be modulated by changing the Fermi energy level (EF) of graphene (through adding external voltage). In addition, the theoretical results derived from the two-particle model are in good agreement with the simulation results based on the finite element method. At high temperature (68 °C), the metasurface mode of operation can be changed to a dual-band absorber, providing absorption of 78.6% and 99.9% at 1.13 THz and 2.16 THz, respectively. Both absorption peaks can be dynamically tuned by changing theEFof graphene. The metasurface is also simultaneously polarization insensitive and has a wide incidence angle. The proposed metasurface can be used as a slow light device with a maximum group delay of 0.5 ps at room temperature and as a refractive index sensor with a maximum sensitivity of 0.5 THz/RIU at high temperature. The designed metasurface offers a new way for designing multifunctional terahertz devices, slow light devices, and refractive index sensors.

11.
Nat Commun ; 14(1): 3476, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37311824

RESUMO

The fascinating collective behaviors of biological systems have inspired extensive studies on shape assembly of robot swarms. Here, we propose a strategy for shape assembly of robot swarms based on the idea of mean-shift exploration: when a robot is surrounded by neighboring robots and unoccupied locations, it would actively give up its current location by exploring the highest density of nearby unoccupied locations in the desired shape. This idea is realized by adapting the mean-shift algorithm, which is an optimization technique widely used in machine learning for locating the maxima of a density function. The proposed strategy empowers robot swarms to assemble highly complex shapes with strong adaptability, as verified by experiments with swarms of 50 ground robots. The comparison between the proposed strategy and the state-of-the-art demonstrates its high efficiency especially for large-scale swarms. The proposed strategy can also be adapted to generate interesting behaviors including shape regeneration, cooperative cargo transportation, and complex environment exploration.

12.
Cancer Med ; 12(4): 4895-4906, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36031798

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and highly malignant thoracic tumor. Although alternative splicing (AS) is associated with tumor prognosis, the prognostic significance of AS in MPM is unknown. METHODS: Transcriptomic data, clinical information, and splicing percentage values for MPM were obtained from The Cancer Genome Atlas (TCGA) and TCGA SpliceSeq databases. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analyses were performed to establish a model affecting the prognosis of MPM. Survival and ROC analyses were used to test the effects of the prognostic model. LASSO/multivariate Cox analysis was used to construct the MPM prognostic splicing factor (SF) model. The SF-AS interaction network was analyzed using Spearman correlation and visualized using Cytoscape. The association between the MPM prognostic SF model and drug sensitivity to chemotherapeutic agents such as cisplatin was analyzed using pRRophetic.R. RESULTS: The LASSO/multivariate Cox analysis identified 41 AS events and 2 SFs that were mostly associated with survival. Nine prognostic prediction models (i.e., seven types of AS model, total AS model, and SF model) were developed. An MPM prognostic SF-AS regulatory network was subsequently constructed with decreased drug sensitivity in the SF model high-risk group (p = 0.025). CONCLUSION: This study provides the first comprehensive analysis of the prognostic value of AS events and SFs in MPM. The SF-AS regulatory network established in this study and our drug sensitivity analysis using the SF model may provide novel targets for pharmacological studies of MPM.


Assuntos
Mesotelioma Maligno , Mesotelioma , Humanos , Prognóstico , Processamento Alternativo , Fatores de Processamento de RNA/genética , Medição de Risco , Mesotelioma/genética
13.
J Agric Food Chem ; 70(41): 13340-13348, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36198124

RESUMO

Acetochlor, an important chloroacetamide herbicide (CAAH) widely used in agriculture, has resulted in environmental contamination, especially of anoxic habitats. In this study, a sulfate-reducing bacterium, designated as SRB-5, was isolated from anaerobic activated sludge and was identified as Cupidesulfovibrio sp. This bacterium possesses a novel anaerobic pathway capable of degrading acetochlor. In this pathway, sulfate is first reduced to sulfide, which attacks the C-Cl bond of acetochlor and abiotically forms acetochlor-thioalcohol and dis-S-acetochlor. These further undergo microbial degradation, producing the intermediates acetochlor ethanesulfonic acid, 2-methyl-6-ethylaniline, and 2-ethylaniline. The degradation half-times of acetochlor (100 µM) by strain SRB-5 were 2.4 and 4.2 days in industrial wastewater and paddy sludge, respectively. Strain SRB-5 could also degrade alachlor, propisochlor, butachlor, pretilachlor, and metolachlor, and the degradation kinetics fit the pseudo-first-order kinetics equation. This work highlights the potential application of strain SRB-5 for the remediation of CAAHs-contaminated sites.


Assuntos
Herbicidas , Herbicidas/metabolismo , Sulfatos , Esgotos/microbiologia , Biodegradação Ambiental , Anaerobiose , Águas Residuárias , Bactérias/metabolismo , Sulfetos
14.
Geriatr Nurs ; 47: 247-253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36007425

RESUMO

This single-arm observational study explored the feasibility and efficacy of a 12-week personalised physical activity and dietary protein intervention programme for older adults undergoing peritoneal dialysis. Older adults undergoing peritoneal dialysis received eight individualised nutrition and physical activity advice sessions provided by trained nurses. Protein intake and physical activity were regarded as primary outcomes. All data were collected at baseline and at week 12. The enrolment rate was 78.4%. Twenty-nine patients participated in the study. Of these, 86.2% (25/29) completed the intervention. There was a significant increase in protein intake (t = -4.453, P< 0.001) and physical activity levels (Z = -2.929, P = 0.004). Of the participants, 56.0% achieved the targeted protein goal, and 41.4% met the physical activity goal. The timed up-and-go performance (t = 4.135, P = 0.001) increased after intervention. Trained nurses can successfully implement personalised diet and physical activity advice, and achieve promising patient outcomes.


Assuntos
Exercício Físico , Diálise Peritoneal , Idoso , Proteínas na Dieta , Estudos de Viabilidade , Humanos , Estado Nutricional
15.
Brief Bioinform ; 23(4)2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35667078

RESUMO

Computational prediction of multiple-type drug-drug interaction (DDI) helps reduce unexpected side effects in poly-drug treatments. Although existing computational approaches achieve inspiring results, they ignore to study which local structures of drugs cause DDIs, and their interpretability is still weak. In this paper, by supposing that the interactions between two given drugs are caused by their local chemical structures (substructures) and their DDI types are determined by the linkages between different substructure sets, we design a novel Substructure-aware Tensor Neural Network model for DDI prediction (STNN-DDI). The proposed model learns a 3-D tensor of $\langle $  substructure, substructure, interaction type  $\rangle $ triplets, which characterizes a substructure-substructure interaction (SSI) space. According to a list of predefined substructures with specific chemical meanings, the mapping of drugs into this SSI space enables STNN-DDI to perform the multiple-type DDI prediction in both transductive and inductive scenarios in a unified form with an explicable manner. The comparison with deep learning-based state-of-the-art baselines demonstrates the superiority of STNN-DDI with the significant improvement of AUC, AUPR, Accuracy and Precision. More importantly, case studies illustrate its interpretability by both revealing an important substructure pair across drugs regarding a DDI type of interest and uncovering interaction type-specific substructure pairs in a given DDI. In summary, STNN-DDI provides an effective approach to predicting DDIs as well as explaining the interaction mechanisms among drugs. Source code is freely available at https://github.com/zsy-9/STNN-DDI.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Redes Neurais de Computação , Coleta de Dados , Interações Medicamentosas , Humanos , Software
16.
Theriogenology ; 186: 135-145, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35468547

RESUMO

We evaluated the effects of different vitrification temperatures (VTs) and cryoprotective agent concentrations (CPAs) on the viability and expressions of long non-coding RNA (lncRNA) in bovine oocytes following vitrification at the germinal vesicle (GV) stage. Our findings provide a theoretical support for improvement of the cryopreservation technology of bovine immature oocytes (BIOs). Bovine cumulus oocyte complexes (COCs) were collected and randomized into five groups: fresh oocytes (control), oocytes vitrified in liquid helium (LHe; -269 °C) with 5.6 M CPAs (LHe 5.6 M), oocytes vitrified in LHe with 6.6 M CPAs (LHe 6.6 M), oocytes vitrified in liquid nitrogen (LN; -196 °C) with 5.6 M CPAs (LN 5.6 M), and oocytes vitrified in LN with 6.6 M CPAs (LN 6.6 M). Of the four vitrification groups, the LHe 5.6 M group exhibited the highest blastocyst rate (13.22%), followed by the LHe 6.6 M group (10.19%) and LN 6.6 M group (9.77%), while the LN 5.6 M group had the lowest blastocyst rate (1.87%). Then, lncRNA expressions in the five groups were profiled. A total of 18,271 lncRNAs were identified, of which 2,158 were differentially expressed lncRNAs (DELs) in the vitrified groups, compared to the fresh group (P < 0.05; fold-change > 2). Co-location (cis) and co-expression (trans) prediction revealed 14 differentially expressed target genes (DETGs), which corresponded to 17 DELs. Based on grouping data and expression profiles of the DELs, we demonstrated that different VTs (-269 °C vs. -196 °C) can affect the expressions of MSTRG.12295.5, MSTRG.37123.1, MSTRG.37930.2, MSTRG.40464.9, MSTRG.8869.3 and MSTRG.26680.6. Expressions of these lncRNAs were affected by CPAs only in the condition of vitrification with LHe (-269 °C). Expressions of MSTRG.35129.6 were associated with exposures to both VTs and CPAs; while expressions of MSTRG.3578.3, MSTRG.40576.3, MSTRG.6723.5, MSTRG.32862.4, MSTRG.1184.4, MSTRG.33110.3, MSTRG.40454.2, MSTRG.41073.2, MSTRG.44732.4 and MSTRG.6729.3 might be related to vitrification. Co-expression analysis showed that MSTRG.12295.5, MSTRG.37930.2, MSTRG.40454.2, MSTRG.8869.3 and MSTRG.6723.5 expressions affect oocyte development after vitrification by regulating target gene expressions. Taken together, improvement of the developmental ability of BIOs after LHe vitrification maybe attributed to changes in expressions of some lncRNAs. Our findings elucidate on the molecular mechanisms underlying the development of BIOs under different VTs and CPAs.


Assuntos
RNA Longo não Codificante , Vitrificação , Animais , Bovinos , Criopreservação/veterinária , Crioprotetores/farmacologia , Oócitos/fisiologia , RNA Longo não Codificante/genética , Temperatura
17.
Environ Res ; 209: 112859, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35114144

RESUMO

Chloroacetamide herbicides (CAAHs) are important herbicides that were widely used to control agricultural weeds. However, their mass applications have seriously contaminated environment, and they are toxic to living beings. CAAHs are easy to enter anoxic environments such as subsoil, wetland sediment, and groundwater, where CAAHs are mainly degraded by anaerobic organisms. To date, there are no research on the anaerobic degradation of CAAHs by pure isolate and toxicity of anaerobic metabolites of CAAHs. In this study, the anaerobic degradation kinetics and metabolites of CAAHs by an anaerobic isolate BAD-10T and the toxicity of anaerobic metabolites were studied. Isolate BAD-10T could degrade alachlor, acetochlor, propisochlor, butachlor, pretilachlor and metolachlor with the degradation kinetics fitting the pseudo-first-order kinetics equation. The degradation rates of CAAHs were significantly affected by the length of N-alkoxyalkyl groups, the shorter the N-alkoxyalkyl groups, the higher the degradation rates. Four metabolites 2-ethyl-6-methyl-N-(ethoxymethyl)-acetanilide (EMEMA), N-(2-methyl-6-ethylphenyl)-acetamide (MEPA), N-2-ethylphenyl acetamide and 2-ethyl-N-carboxyl aniline were identified during acetochlor degradation, and an anaerobic catabolic pathway of acetochlor was proposed. The toxicity of EMEMA and EMPA for zebrafish, Arabidopsis and Chlorella ellipsoidea were obviously lower than that of acetochlor, indicating that the anaerobic degradation of acetochlor by isolate BAD-10T is a detoxification process. The work reveals the anaerobic degradation kinetics and catabolic pathway of CAAHs and highlights a potential application of Proteiniclasticum sediminis BAD-10T for bioremediation of CAAHs residue-contaminated environment.


Assuntos
Chlorella , Herbicidas , Acetamidas/metabolismo , Acetamidas/toxicidade , Anaerobiose , Animais , Biodegradação Ambiental , Chlorella/metabolismo , Herbicidas/toxicidade , Peixe-Zebra/metabolismo
18.
Kaohsiung J Med Sci ; 38(5): 403-414, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35146902

RESUMO

Accumulating evidence indicates that long noncoding RNAs (lncRNAs) act as tumor promoters or suppressors in various types of cancer. Previous investigations suggest that ceramide synthase 6 (CERS6) antisense RNA 1 (CERS6-AS1) acts as an oncogene in breast cancer; however, its role in colorectal cancer is unknown. This study aimed to explore the molecular mechanism of CERS6-AS1 in colorectal cancer. Gene expression in colorectal cancer was examined using reverse transcription-quantitative polymerase chain reaction and western blot analyses. The viability and proliferation of colorectal cancer cells were measured by Cell Counting Kit-8 assays and colony formation assays. The migratory and invasive capacities of the colorectal cancer cells were assessed by Transwell assay. Cell stemness was examined by sphere-formation assay. Mechanistically, RNA pull-down assays, RNA immunoprecipitation assays, and luciferase reporter assays were performed to explore the relationship among CERS6-AS1, miR-15b-5p and spectrin beta, non-erythrocytic 2 (SPTBN2). Moreover, a xenograft tumor model was established to investigate the role of CERS6-AS1 in vivo. We found that CERS6-AS1 and SPTBN2 were highly expressed in colorectal cancer tissues and cells. CERS6-AS1 depletion inhibited cell viability, proliferation, migration, and invasion; the epithelial-mesenchymal transition process and stemness. It suppressed xenograft tumor growth in colorectal cancer. Moreover, SPTBN2 levels were positively regulated by CERS6-AS1 and negatively regulated by miR-15b-5p in colorectal cancer cells. Rescue assays revealed that SPTBN2 reversed the inhibitory effect of CERS6-AS1 deficiency on the malignant behaviors of colorectal cancer cells. Overall, the lncRNA CERS6-AS1 facilitates malignant phenotypes of colorectal cancer cells by targeting miR-15b-5p to upregulate SPTBN2.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Antissenso/genética , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fenótipo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Espectrina/genética , Esfingosina N-Aciltransferase/genética , Esfingosina N-Aciltransferase/metabolismo
19.
Carbohydr Res ; 512: 108498, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35074663

RESUMO

Selenium polysaccharides have antioxidant, anti-tumor and other activities. Tea selenium polysaccharides and Lentinan selenium polysaccharides, etc. have been studied. Pennycress is a super-rich selenium plant and there are few studies about pennycress selenium-containing polysaccharides. In this study, the following researches were carried out on pennycress selenium polysaccharides: Selenium-containing polysaccharides were extracted from the leaves of pennycress (Thlaspi arvense L.) using an efficient subcritical water extraction (SWE) process. After purification, two fractions (Se-PPS1 and Se-PPS3) were obtained and subjected to structural identification. The results showed that the molecular weights of Se-PPS1 and Se-PPS3 were 4.2 × 104 Da and 4.5 × 104 Da, respectively. Se-PPS1 is mainly comprised of glucose, galactose, and xylose. Se-PPS3 consists of glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, xylose, and arabinose. Fourier transform infrared spectroscopy (FT-IR) analysis showed that the two fractions had absorption spectra typical of selenium esters and spectral characteristics of polysaccharides. The glycosidic linkages were determined by Gas chromatography-mass spectrometry (GC-MS) and Nuclear magnetic resonance (NMR). The two fractions have (1 â†’ 6)-ß-D- Galp and T-α-D- Glcp configurations. Moreover, in vitro antioxidant activity assays showed that Se-PPS1 and Se-PPS3 exhibited effective radical-scavenging abilities, suggesting they have potential applications as natural antioxidants in food and medicine.


Assuntos
Selênio , Thlaspi , Antioxidantes/química , Polissacarídeos/química , Selênio/análise , Selênio/química , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Foods ; 11(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37430935

RESUMO

The processing of Acanthopanax sessiliflorus has attracted interest due to its health benefits. In this work, an emerging blanching technology, called hot-air flow rolling dry-blanching (HMRDB), was employed to treat A. sessiliflorus before drying. The effects of varied blanching times (2-8 min) on enzyme inactivation, drying characteristics, bioactive compound retention, and microstructure were examined. The results demonstrated that blanching for 8 min rendered polyphenol oxidase and peroxidase nearly inactive. The blanching process reduced the drying time of samples by up to 57.89% compared to an unblanched sample. The Logarithmic model showed good fitting performance for the drying curves. The total phenolic and flavonoid content of the dried product increased as blanching time increased. The total anthocyanin content of the samples blanched for 6 min was 3.9 times higher than that of the unblanched samples, and 8 min of blanching produced the greatest DPPH• and ABTS• scavenging capabilities. The retention of active compounds in a dried product is a result of the inactivation of enzymes and a reduced drying period. Changes in the porous structure of the blanched samples would be responsible for the accelerated drying rate, according to microstructural analysis. These results indicate that HMRDB enhances the drying process and improves drying quality when applied to A. sessiliflorus before drying.

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