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1.
J Biol Chem ; 299(11): 105329, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37805139

RESUMEN

Prion diseases are a group of transmissible neurodegenerative diseases primarily caused by the conformational conversion of prion protein (PrP) from α-helix-dominant cellular prion protein (PrPC) to ß-sheet-rich pathological aggregated form of PrPSc in many mammalian species. Dogs exhibit resistance to prion diseases, but the mechanism behind the phenomenon remains poorly understood. Compared with human PrP and mouse PrP, dog PrP has two unique amino acid residues, Arg177 and Asp159. Because PrPC contains a low-complexity and intrinsically disordered region in its N-terminal domain, it undergoes liquid-liquid phase separation (LLPS) in vitro and forms protein condensates. However, little is known about whether these two unique residues modulate the formation of PrPC condensates. Here, using confocal microscopy, fluorescence recovery after photobleaching assays, thioflavin T binding assays, and transmission electron microscopy, we report that Arg177 and Asp159 from the dog PrP slow the LLPS of full-length human PrPC, shifting the equilibrium phase boundary to higher protein concentrations and inhibit amyloid formation of the human protein. In sharp contrast, His177 and Asn159 from the human PrP enhance the LLPS of full-length dog PrPC, shifting the equilibrium phase boundary to lower protein concentrations, and promote fibril formation of the canid protein. Collectively, these results demonstrate how LLPS and amyloid formation of PrP are inhibited by a single residue Arg177 or Asp159 associated with prion disease resistance, and how LLPS and fibril formation of PrP are promoted by a single residue His177 or Asn159. Therefore, Arg177/His177 and Asp159/Asn159 are key residues in modulating PrPC liquid-phase condensation.


Asunto(s)
Enfermedades por Prión , Priones , Ratones , Perros , Humanos , Animales , Proteínas Priónicas/metabolismo , Priones/metabolismo , Amiloide/química , Proteínas Amiloidogénicas , Mamíferos/metabolismo
2.
Entropy (Basel) ; 26(2)2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38392427

RESUMEN

Compound droplets have received increasing attention due to their applications in many several areas, including medicine and materials. Previous works mostly focused on compound droplets on planar surfaces and, as such, the effects of curved walls have not been studied thoroughly. In this paper, the influence of the properties of curved solid wall (including the shape, curvature, and contact angle) on the wetting behavior of compound droplets is explored. The axisymmetric lattice Boltzmann method, based on the conservative phase field formulation for ternary fluids, was used to numerically study the wetting and spreading of a compound droplet of the Janus type on various curved solid walls at large density ratios, focusing on whether the separation of compound droplets occurs. Several types of wall geometries were considered, including a planar wall, a concave wall with constant curvature, and a convex wall with fixed or variable curvature (specifically, a prolate or oblate spheroid). The effects of surface wettability, interfacial angles, and the density ratio (of droplet to ambient fluid) on the wetting process were also explored. In general, it was found that, under otherwise identical conditions, droplet separation tends to happen more likely on more hydrophilic walls, under larger interfacial angles (measured inside the droplet), and at larger density ratios. On convex walls, a larger radius of curvature of the surface near the droplet was found to be helpful to split the Janus droplet. On concave walls, as the radius of curvature increases from a small value, the possibility to observe droplet separation first increases and then decreases. Several phase diagrams on whether droplet separation occurs during the spreading process were produced for different kinds of walls to illustrate the influences of various factors.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38652217

RESUMEN

Thrombus age determination in fatal venous thromboembolism cases is an important task for forensic pathologists. In this study, we investigated the time-dependent expressions of formyl peptide receptor 2 (FPR2) and Annexin A1 (ANXA1) in a stasis-induced deep vein thrombosis (DVT) murine model, with the aim of obtaining useful information for thrombus age timing. A total of 75 ICR mice were randomly classified into thrombosis group and control group. In thrombosis group, a DVT model was established by ligating the inferior vena cava (IVC) of mice, and thrombosed IVCs were harvested at 1, 3, 5, 7, 10, 14, and 21 days after modeling. In control group, IVCs without thrombosis were taken as control samples. The expressions of FPR2 and ANXA1 during thrombosis were detected using immunohistochemistry and double immunofluorescence staining. Their protein and mRNA levels in the samples were determined by Western blotting and quantitative real-time PCR. The results reveal that FPR2 was predominantly expressed by intrathrombotic neutrophils and macrophages. ANXA1 expression in the thrombi was mainly distributed in neutrophils, endothelial cells of neovessels, and fibroblastic cells. After thrombosis, the expressions of FPR2 and ANXA1 were time-dependently up-regulated. The percentage of FPR2-positive cells and the level of FPR2 protein significantly elevated at 1, 3, 5 and 7 days after IVC ligation as compared to those at 10, 14 and 21 days after ligation (p < 0.05). Moreover, the mRNA level of FPR2 were significantly higher at 5 days than that at the other post-ligation intervals (p < 0.05). Besides, the levels of ANXA1 mRNA and protein peaked at 10 and 14 days after ligation, respectively. A significant increase in the mRNA level of ANXA1 was found at 10 and 14 days as compared with that at the other post-ligation intervals (p < 0.01). Our findings suggest that FPR2 and ANXA1 are promising as useful markers for age estimation of venous thrombi.

4.
Fa Yi Xue Za Zhi ; 40(2): 179-185, 2024 Apr 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38847034

RESUMEN

OBJECTIVES: To detect the expression changes of interleukin-10 (IL-10) and transforming growth factor-ß1 (TGF-ß1) during the development of deep vein thrombosis in mice, and to explore the application value of them in thrombus age estimation. METHODS: The mice in the experimental group were subjected to ligation of inferior vena cava. The mice were sacrificed by excessive anesthesia at 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 21 d after ligation, respectively. The inferior vena cava segment with thrombosis was extracted below the ligation point. The mice in the control group were not ligated, and the inferior vena cava segment at the same position as the experimental group was extracted. The expression changes of IL-10 and TGF-ß1 were detected by immunohistochemistry (IHC), Western blotting and real-time qPCR. RESULTS: IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-ß1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis. Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-ß1 in each experimental group were higher than those in the control group. The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation, respectively. The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group, and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group. The mRNA and protein levels of TGF-ß1 reached the peak at 10 d and 14 d after ligation, respectively. The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group, and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group. CONCLUSIONS: The expressions of IL-10 and TGF-ß1 during the evolution of deep vein thrombosis present time-dependent sequential changes, and the expression levels of IL-10 and TGF-ß1 can provide a reference basis for thrombus age estimation.


Asunto(s)
Modelos Animales de Enfermedad , Inmunohistoquímica , Interleucina-10 , Factor de Crecimiento Transformador beta1 , Vena Cava Inferior , Trombosis de la Vena , Animales , Interleucina-10/metabolismo , Interleucina-10/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Trombosis de la Vena/metabolismo , Trombosis de la Vena/etiología , Ratones , Vena Cava Inferior/metabolismo , Vena Cava Inferior/patología , Masculino , Factores de Tiempo , Monocitos/metabolismo , Western Blotting , ARN Mensajero/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Ligadura , Fibroblastos/metabolismo
5.
Wound Repair Regen ; 28(6): 772-779, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32856346

RESUMEN

Impaired wound healing is a common complication of diabetes. In diabetic wounds, macrophages present dysfunctional efferocytosis and abnormal phenotypes, which could result in excessive neutrophil accumulation and prolonged inflammation, thereby eventually hindering wound repair. ANXA1 N-terminal peptide Ac2-26 exhibits a high potential in mitigating inflammation and improving repair; however, its efficacy in diabetic wound repair remains unclear. In this study, a cutaneous excisional wound model was built in genetically diabetic mice. Ac2-26 or a vehicle solution was employed locally in wound sites. Subsequently, wound zones were measured and sampled at different time intervals post-wounding. Using hematoxylin-eosin and Masson's trichrome staining, we observed the histopathological variations and collagen deposition in wound samples. Based on immunohistochemistry and immunofluorescence, the numbers of neutrophils, macrophages, and CD206-positive macrophages in the wound samples were determined. Cytokine expression in wound samples was studied by immunoblot assay. Results showed that Ac2-26 treatment could facilitate diabetic wound closure, down-regulate the number of neutrophils, and improve angiogenesis and collagen deposition. In addition, Ac2-26 application expedited macrophage recruitment and up-regulated the percentage of macrophages expressing CD206, which is a marker for M2 macrophages. Moreover, Ac2-26 inhibited the expressions of TNF-α and IL-6 and up-regulated the expressions of IL-10, TGF-ß, and VEGFA during diabetic wound healing. Hence, based on the aforementioned findings, Ac2-26 application in diabetic wounds could exert anti-inflammatory and pro-repair effects by reducing neutrophil accumulation and facilitating M2 macrophage development.


Asunto(s)
Anexina A1/farmacología , Diabetes Mellitus Experimental/complicaciones , Macrófagos/patología , Péptidos/farmacología , Piel/lesiones , Traumatismos de los Tejidos Blandos/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Citocinas/metabolismo , Diabetes Mellitus Experimental/patología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Piel/efectos de los fármacos , Piel/patología , Traumatismos de los Tejidos Blandos/complicaciones , Traumatismos de los Tejidos Blandos/patología , Resultado del Tratamiento
6.
Langmuir ; 34(47): 14186-14195, 2018 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-30433785

RESUMEN

Coalescence-induced droplet jumping from a round hydrophobic fiber was studied by phase-field-based hybrid lattice-Boltzmann finite-difference simulations in which the interface dynamics is handled by the finite-difference solution of the Cahn-Hilliard equation and the hydrodynamics is handled by the lattice-Boltzmann method. It was found that at a small Ohnesorge number of O(0.01), several different outcomes, including normal jumping at a positive velocity, jumping with a negative velocity, jumping after wrapping the fiber, and oscillating on the fiber, may occur after droplet coalescence, depending on the wettability of the fiber and the droplet-to-fiber radius ratio. In accordance with previous reports, normal droplet jumping from the fiber happens only when the radius ratio exceeds some critical value for a given contact angle. The critical radius ratio decreases as the fiber becomes more hydrophobic. For a given contact angle and radius ratio, it was observed that there exists an Ohnesorge number at which the jumping speed achieves a maximum value.

7.
Eur Phys J E Soft Matter ; 41(2): 17, 2018 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-29404782

RESUMEN

We propose an alternative method to implement the contact angle boundary condition on a solid wall and apply it in hybrid lattice-Boltzmann finite-difference simulations of two-phase flows with immersed surfaces in which the flow equations are solved by the lattice-Boltzmann method and the interface equations are solved by the finite-difference method. Using the hyperbolic tangent profile of the order parameter across an interface in phase-field theory, we were able to obtain its unknown value at a ghost point from the information at only one point in the fluid domain. This is in contrast with existing approaches relying on interpolations involving several points. The special feature allows it to be more easily implemented on immersed surfaces cutting through the grid lines. It was properly incorporated into the framework of the hybrid lattice-Boltzmann finite-difference simulation, and applied successfully for several problems with different levels of complexity. First, the equilibrium shapes of a droplet on a sphere with different contact angles and radii were studied under cylindrical geometry and a good agreement with theoretical predictions was found. Preliminary studies on a three-dimensional droplet spreading on a sphere were also performed and the results agreed well with the corresponding axisymmetric results. Second, the spreading of a two-dimensional drop on an embedded inclined wall with a given contact angle was investigated and the results matched those on a flat wall at the domain boundary under the same condition. Third, capillary filling in a cylindrical tube was studied and the speed of the interface in the tube was found to follow Washburn's law. Fourth, a droplet impacting on a sphere was investigated and several different outcomes were captured depending on the Reynolds number, the viscosity ratio, and the wettability and radius of the sphere. Finally, the proposed method was shown to be capable of studying even more complicated problems involving the interaction between a droplet and multiple objects of different sizes and contact angles.

8.
Hepatobiliary Pancreat Dis Int ; 17(3): 204-209, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29807766

RESUMEN

BACKGROUND: Previous studies have emphasized the need to reduce tacrolimus (TAC) trough levels in the early post-liver transplantation (LT) period. However, whether late-period TAC trough levels influence the long-term outcomes of liver recipients is not clear. METHODS: We enrolled 155 adult liver recipients survived more than 3 years after living donor liver transplantation because of non-malignant liver diseases. The maintenance immunosuppressive regimens were TAC monotherapy and combined therapy with mycophenolate mofetil. Patients were divided into three groups according to their late-period TAC trough levels: < 3 ng/mL group, 3-5 ng/mL group, and  >5 ng/mL group. The complications and adverse effects of TAC were analyzed. RESULTS: Each group showed similar rejection, graft loss and mortality. Patients achieved the < 5 ng/mL state in less than 4 years had fewer new-onset diabetes, hyperlipidemia, de novo malignancies, and hepatitis B virus recurrence; the complications of renal dysfunction and hypertension rates were the same among these 3 groups. CONCLUSIONS: Collectively, our findings indicated that lower TAC trough levels in the late period of liver transplantation are safe, improve the long-term outcomes.


Asunto(s)
Inhibidores de la Calcineurina/sangre , Inmunosupresores/sangre , Trasplante de Hígado/métodos , Donadores Vivos , Tacrolimus/sangre , Adulto , Anciano , Inhibidores de la Calcineurina/administración & dosificación , Inhibidores de la Calcineurina/efectos adversos , Inhibidores de la Calcineurina/farmacocinética , Monitoreo de Drogas , Quimioterapia Combinada , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/farmacocinética , Estimación de Kaplan-Meier , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Tacrolimus/farmacocinética , Resultado del Tratamiento , Adulto Joven
9.
J Oral Maxillofac Surg ; 75(7): 1476.e1-1476.e15, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28412268

RESUMEN

PURPOSE: Third molars (M3s) have been hypothesized to be associated with the risk of mandibular angle fracture and mandibular condylar fracture. The authors systematically estimated the relative risk (RR) of M3 status for the development of mandibular angle fracture and mandibular condylar fracture through a meta-analysis of cohort studies. MATERIALS AND METHODS: In this systematic review, the PubMed, EMBASE, and Cochrane Library databases were searched from inception to October 2016. The predictor of risk was the presence or absence of M3s. The primary outcome was the RR of mandibular angle or condylar fracture. A fixed- or a random-effects model was applied to evaluate the pooled risk estimates. Sensitivity analysis also was performed to identify the potential sources of heterogeneity. Publication bias was assessed by the Begg and Egger tests. RESULTS: Overall, 13 retrospective cohort studies were included. Of these, 13 reported the association between M3s and mandibular angle fracture, and 5 reported the association with mandibular condylar fracture. Patients with M3s had an increased risk of mandibular angle fractures (RR = 2.63; 95% confidence interval [CI], 2.15-3.21) but a decreased risk of mandibular condylar fractures (RR = 0.47; 95% CI, 0.25-0.86). Substantial heterogeneity in the risk estimates was found. No evidence of publication bias was found. CONCLUSION: The present meta-analysis provides further evidence associating the presence of M3s with an increased risk of mandibular angle fractures and a simultaneously decreased risk of mandibular condylar fracture. Because of potentially more serious complications associated with condylar fracture, clinicians should carefully consider the decision to remove M3s to decrease the risk of mandibular angle fracture.


Asunto(s)
Cóndilo Mandibular/lesiones , Fracturas Mandibulares/epidemiología , Tercer Molar , Estudios de Cohortes , Humanos , Medición de Riesgo
11.
Am J Chin Med ; 52(2): 493-512, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38480500

RESUMEN

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.


Asunto(s)
Colitis , Eugenol , Animales , Ratones , Eugenol/farmacología , Eugenol/uso terapéutico , Factor 88 de Diferenciación Mieloide/genética , Receptor Toll-Like 4/genética , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Proteínas Adaptadoras Transductoras de Señales , Colon , Citocinas , Macrófagos , Antiinflamatorios , Sulfato de Dextran , FN-kappa B , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
12.
IEEE Trans Neural Netw Learn Syst ; 34(9): 5366-5380, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35439147

RESUMEN

In this article, we propose a novel solution for nonconvex problems of multiple variables, especially for those typically solved by an alternating minimization (AM) strategy that splits the original optimization problem into a set of subproblems corresponding to each variable and then iteratively optimizes each subproblem using a fixed updating rule. However, due to the intrinsic nonconvexity of the original optimization problem, the optimization can be trapped into a spurious local minimum even when each subproblem can be optimally solved at each iteration. Meanwhile, learning-based approaches, such as deep unfolding algorithms, have gained popularity for nonconvex optimization; however, they are highly limited by the availability of labeled data and insufficient explainability. To tackle these issues, we propose a meta-learning based alternating minimization (MLAM) method that aims to minimize a part of the global losses over iterations instead of carrying minimization on each subproblem, and it tends to learn an adaptive strategy to replace the handcrafted counterpart resulting in advance on superior performance. The proposed MLAM maintains the original algorithmic principle, providing certain interpretability. We evaluate the proposed method on two representative problems, namely, bilinear inverse problem: matrix completion and nonlinear problem: Gaussian mixture models. The experimental results validate the proposed approach outperforms AM-based methods.

13.
Neural Netw ; 165: 333-343, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37327580

RESUMEN

Multi-view subspace clustering has attracted great attention due to its ability to explore data structure by utilizing complementary information from different views. Most of existing methods learn a sample representation coefficient matrix or an affinity graph for each single view, then the final clustering result is obtained from the spectral embedding of a consensus graph using certain traditional clustering techniques, such as k-means. However, clustering performance will be degenerated if the early fusion of partitions cannot fully exploit relationships between all samples. Different from existing methods, we propose a multi-view subspace clustering method via adaptive graph learning and late fusion alignment (AGLLFA). For each view, AGLLFA learns an affinity graph adaptively to capture the similarity relationship among samples. Moreover, a spectral embedding learning term is designed to exploit the latent feature space of different views. Furthermore, we design a late fusion alignment mechanism to generate an optimal clustering partition by fusing view-specific partitions obtained from multiple views. An alternate updating algorithm with validated convergence is developed to solve the resultant optimization problem. Extensive experiments on several benchmark datasets are conducted to illustrate the effectiveness of the proposed method when compared with other state-of-the-art methods. The demo code of this work is publicly available at https://github.com/tangchuan2000/AGLLFA.


Asunto(s)
Algoritmos , Aprendizaje , Benchmarking , Análisis por Conglomerados , Consenso
14.
Food Funct ; 14(13): 5977-5993, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37334912

RESUMEN

Clinical evidence suggests that a bidirectional relationship is present between sleep loss and psychiatric disorders. Both melatonin receptor agonist ramelteon (RMT) and n-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit antidepressant effects, while their underlying molecular mechanisms might be different. Thus, the present study aims to investigate the add-on effects and possible mechanisms of how RMT and different n-3 PUFAs modulate the melatonin receptor pathway as well as brain lipidome to ameliorate the neuropsychiatric behaviors displayed in rats under chronic sleep deprivation. Thirty-one 6-week-old male Wistar rats were divided into five groups: control (C), sleep deprivation (S), sleep deprivation treated with RMT (SR), sleep deprivation treated with RMT and eicosapentaenoic acid (C20:5n-3, EPA) (SRE), and sleep deprivation treated with RMT and docosahexaenoic acid (C22:6n-3, DHA) (SRD) groups. The results reveal that RMT plus EPA alleviated depressive-like behavior when the rats were subjected to the forced swimming test, whereas RMT plus DHA alleviated anxiety-like behavior when the rats were subjected to the elevated plus maze test. The results of a western blot analysis further revealed that compared with the rats in the S group, those in the SRE and SRD groups exhibited a significantly increased expression of MT2 in the prefrontal cortex, with greater benefits observed in the SRE group. In addition, decreased BDNF and TrkB expression levels were upregulated only in the SRE group. Lipidomic analysis further revealed possible involvement of aberrant lipid metabolism and neuropsychiatric behaviors. RMT plus EPA demonstrated promise as having the effects of reversing the levels of the potential biomarkers of depressive-like behaviors. RMT plus EPA or DHA could ameliorate depressive- and anxiety-like behaviors in sleep-deprived rats through the alteration of the lipidome and MT2 receptor pathway in the brain, whereas EPA and DHA exerted a differential effect.


Asunto(s)
Ácidos Grasos Omega-3 , Ratas , Masculino , Animales , Ácidos Grasos Omega-3/farmacología , Lipidómica , Privación de Sueño/tratamiento farmacológico , Receptores de Melatonina , Ratas Wistar , Encéfalo , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/uso terapéutico , Ácidos Docosahexaenoicos/farmacología , Ácidos Grasos Insaturados/farmacología
15.
Ying Yong Sheng Tai Xue Bao ; 34(9): 2489-2497, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37899116

RESUMEN

Constructing ecological security pattern and identifying ecological important areas are the focus of current research on regional ecological security. With Ningbo City as a case study area, we identified ecological sources by remote sensing ecological index, the ecological corridors and pinch point by circuit theory model, and the minimum spanning tree and cuts by graph theory algorithm. The results showed that there were 203 ecological sources in Ningbo, and that the main type of land cover was forest, including a small amount of paddy fields and flooded vegetation. There were 368 ecological corridors with a total length of 573.42 km, being dense in the southwest and sparse in the northeast. There were 91 ecological pinch points, which mainly distributed between coastal areas and closely related ecological sources. According to current situation, we put forward the optimization strategy with 187 primary corridors, 181 secondary corridors, 50 ecological restoration priority areas and 59 long-term ecological restoration areas. The optimization strategy combined with graph theory and circuit theory model would provide a refe-rence for the constructing of ecological security pattern.


Asunto(s)
Ecología , Ecosistema , Conservación de los Recursos Naturales , Tecnología de Sensores Remotos , Bosques
16.
J Med Chem ; 66(1): 371-383, 2023 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-36598095

RESUMEN

Inadequate bioavailability is one of the most critical reasons for the failure of oral drug development. However, the way that substructures affect bioavailability remains largely unknown. Serotonin transporter (SERT) inhibitors are first-line drugs for major depression disorder, and improving their bioavailability may be able to decrease side-effects by reducing daily dose. Thus, it is an excellent model to probe the relationship between substructures and bioavailability. Here, we proposed the concept of "nonbioavailable substructures", referring to substructures that are unfavorable to bioavailability. A machine learning model was developed to identify nonbioavailable substructures based on their molecular properties and shows the accuracy of 83.5%. A more potent SERT inhibitor DH4 was discovered with a bioavailability of 83.28% in rats by replacing the nonbioavailable substructure of approved drug vilazodone. DH4 exhibits promising anti-depression efficacy in animal experiments. The concept of nonbioavailable substructures may open up a new venue for the improvement of drug bioavailability.


Asunto(s)
Trastorno Depresivo Mayor , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Ratas , Animales , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Disponibilidad Biológica , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/química , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Trastorno Depresivo Mayor/tratamiento farmacológico
18.
Foods ; 11(9)2022 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-35564085

RESUMEN

We established and validated a sensitive multi-residue analytical method for identifying benzophenone (BP) and nine BP derivatives (2,4-dihydroxybenzophenone [BP-1], 2,2',4,4'-tetrahydroxydroxybenzophenone, 2-hydroxy-4-methoxy benzophenone, 2,2'-dihydroxy 4-methoxy benzophenone, 2-hydroxybenzophenone [2-OHBP], 4-hydroxybenzophenone, 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl). Solid−liquid extraction pretreatment and ultra-high-performance liquid chromatography−tandem mass spectrometry (UHPLC−MS/MS) were employed in an analysis of 85 packaged cereal-based food samples (25 pastry, 50 rice, and 10 noodle samples). The method had satisfactory linearity (R2 ≥ 0.995), low limits of detection (pastry: 0.02−4.2 ng/g; rice and noodle: 0.02−2 ng/g), and favorable precision, with within-run and between-run coefficient of variation ranges of 1−29% and 1−28%, respectively. BP and 4-MBP were detected in 100% of the pastry samples, and BP-1 and 2-OHBP were found in 76% and 56% of the pastry samples, respectively. BP and 2-OHBP were found in 92% and 38% of the rice samples, respectively. BP was found in 50% of the noodle samples. BP contributed the most to the total level of BPs in pastries, with significantly higher mean ± standard deviation (range) levels for pastries (26.8 ± 32.6 [1.8−115.4] ng/g) than rice (1.2 ± 2.0 [0.4−13.4] ng/g) and noodles (0.7 ± 0.7 [0.4−1.9] ng/g); p < 0.0001). The trace levels of 4-MBP identified in the samples demonstrate the need for the development of analytical methods with high sensitivity and specificity; the proposed method satisfies this need.

19.
IEEE Trans Image Process ; 31: 4377-4392, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35759598

RESUMEN

Image denoising aims to restore a clean image from an observed noisy one. Model-based image denoising approaches can achieve good generalization ability over different noise levels and are with high interpretability. Learning-based approaches are able to achieve better results, but usually with weaker generalization ability and interpretability. In this paper, we propose a wavelet-inspired invertible network (WINNet) to combine the merits of the wavelet-based approaches and learning-based approaches. The proposed WINNet consists of K -scale of lifting inspired invertible neural networks (LINNs) and sparsity-driven denoising networks together with a noise estimation network. The network architecture of LINNs is inspired by the lifting scheme in wavelets. LINNs are used to learn a non-linear redundant transform with perfect reconstruction property to facilitate noise removal. The denoising network implements a sparse coding process for denoising. The noise estimation network estimates the noise level from the input image which will be used to adaptively adjust the soft-thresholds in LINNs. The forward transform of LINNs produces a redundant multi-scale representation for denoising. The denoised image is reconstructed using the inverse transform of LINNs with the denoised detail channels and the original coarse channel. The simulation results show that the proposed WINNet method is highly interpretable and has strong generalization ability to unseen noise levels. It also achieves competitive results in the non-blind/blind image denoising and in image deblurring.

20.
Foods ; 11(4)2022 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-35206047

RESUMEN

A fast, robust, and sensitive analytical method was developed and validated for the simultaneous identification of benzophenone (BP) and nine BP analogs (BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone, 4-hydroxybenzophenone, 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl) in 25 samples of rice cereal. Fast pesticide extraction (FaPEx) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry was applied. The developed method exhibited satisfactory linearity (r > 0.997), favorable recoveries between 71% and 119%, and a limit of detection ranging from 0.001 to 0.5 ng/g. The detection frequencies of BP, 4-MBP, and BP-3 were 100%, 88%, and 52%, respectively. BP had higher geometric levels, with a mean of 39.8 (19.1-108.9) ng/g, and 4-MBP had low levels, with a mean of 1.9 (1.3-3.3) ng/g. The method can be applied to routine rice cereal analysis at the nanogram-per-gram level. For infants aged 0-3 years, the hazard quotients of BP and 4-MBP were lower than one, and the margin of exposure for BP was higher than 10,000, suggesting that rice cereal consumption poses no health concern for Taiwanese infants.

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