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1.
Appl Radiat Isot ; 212: 111423, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38981165

RESUMO

The dose effect of radiation has long been a topic of concern, but the molecular mechanism behind it is still unclear. In this study, dried pea seeds were irradiated with 252Cf fission neutron source. Through analyzing the transcriptome and proteome of M1 generation pea (Pisum sativum L.) leaves, we studied the molecular rule and mechanism of neutron dose effect. Our results showed three important rules of global gene expression in the studied dose range. The rule closely related to the neutron absorbed dose at the transcription and translation levels is: the greater the difference in neutron absorbed dose between two radiation treatment groups, the greater the difference in differential expression between the two groups and the control group. We also obtained important sensitive metabolic pathways of neutron radiation, as well as related key genes. Furthermore, the overall molecular regulation mechanism of dose effect was revealed based on the main functional items obtained. Our research results can be applied to appropriate radiation dose estimation and agricultural production practice.

2.
Phys Eng Sci Med ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008261

RESUMO

An improved Finite Element Model(FEM) is applied to compare the biomechanical stability of plates with three different options in the treatment of distal fibula fractures in this study. The Computed Tomography(CT) scan of the knee to ankle segment of a volunteer was performed. A 3D fibula FEM was reconstructed based on the CT data. Three different loads (uni-pedal standing, torsion, and twisting) were applied, the same as in the experiments in the literature. The stresses and strains of the three options were compared under the same loads, using a 4-hole locking plate (Option A), a 5-hole locking plate (Option B), and a 6-hole locking plate (Option C) in a standard plate for lateral internal fixation. The simulation results show that all three options showed a stress masking effect. Option C had the best overall biomechanical performance and could effectively distribute the transferred weight. This is because option C has greater torsional stiffness and better biomechanical stability than options A and B, and therefore, option C is the recommended internal fixation method for distal fibula fractures. The Finite Element Analysis(FEA) method developed in this work applies to the stress analysis of fracture treatment options in other body parts.

3.
Ren Fail ; 46(2): 2367705, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39010847

RESUMO

Previous studies indicate a strong correlation between the incidence of chronic kidney disease (CKD) and lower economic status. However, these studies often struggle to delineate a clear cause-effect relationship, leaving healthcare providers uncertain about how to manage kidney disease in a way that improves patients' financial outcomes. Our study aimed to explore and establish a causal relationship between CKD and socioeconomic status, identifying critical influencing factors. We utilized summary meta-analysis data from the CKDGen Consortium and UK Biobank. Genetic variants identified from these sources served as instrumental variables (IVs) to estimate the association between CKD and socioeconomic status. The presence or absence of CKD, estimated glomerular filtration rate (eGFR), and albuminuria were used as exposures, while income and regional deprivation were analyzed as outcomes. We employed the R packages 'TwoSampleMR' and 'Mendelianrandomization' to conduct both univariable and multivariable Mendelian randomization (MR) analyses, assessing for potential pleiotropy and heterogeneity. Our univariable MR analysis revealed a significant causal relationship between high levels of albuminuria and lower income (OR = 0.84, 95% CI: 0.73-0.96, p = 0.013), with no significant pleiotropy detected. In the multivariable MR analysis, both CKD (OR = 0.867, 95% CI: 0.786-0.957, p = 0.0045) and eGFR (OR = 0.065, 95% CI: 0.010-0.437, p = 0.0049) exhibited significant effects on income. This study underscores that higher albuminuria levels in CKD patients are associated with decreased income and emphasizes the importance of effective management and treatment of albuminuria in CKD patients to mitigate both social and personal economic burdens.


Assuntos
Albuminúria , Taxa de Filtração Glomerular , Análise da Randomização Mendeliana , Insuficiência Renal Crônica , Classe Social , Humanos , Insuficiência Renal Crônica/complicações
4.
iScience ; 27(7): 110202, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38993674

RESUMO

Time-restricted eating (TRE) is a promising obesity management strategy, but weight-loss efficacy varies among participants, and the underlying mechanism is unclear. The study aimed to investigate the role of gut microbiota in weight-loss response during long-term TRE intervention. We analyzed data from 51 obese adults in a 12-month TRE program, categorizing them into distinct weight loss groups (DG) and moderate weight loss groups (MG) based on their TRE responses. Shotgun metagenomic sequencing analysis revealed a significant increase in species closely associated with weight loss effectiveness and metabolic parameter changes in the DG group. Pathways related to fatty acid biosynthesis, glycogen biosynthesis, and nucleotide metabolism were reduced in the DG group and enhanced in the MG group. Next, we identified nine specific species at baseline that contributed better responses to TRE intervention and significant weight loss. Collectively, gut microbiota contributes to responsiveness heterogeneity in TRE and can predict weight-loss effectiveness.

5.
Med Image Anal ; 97: 103213, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38850625

RESUMO

Multi-modal data can provide complementary information of Alzheimer's disease (AD) and its development from different perspectives. Such information is closely related to the diagnosis, prevention, and treatment of AD, and hence it is necessary and critical to study AD through multi-modal data. Existing learning methods, however, usually ignore the influence of feature heterogeneity and directly fuse features in the last stages. Furthermore, most of these methods only focus on local fusion features or global fusion features, neglecting the complementariness of features at different levels and thus not sufficiently leveraging information embedded in multi-modal data. To overcome these shortcomings, we propose a novel framework for AD diagnosis that fuses gene, imaging, protein, and clinical data. Our framework learns feature representations under the same feature space for different modalities through a feature induction learning (FIL) module, thereby alleviating the impact of feature heterogeneity. Furthermore, in our framework, local and global salient multi-modal feature interaction information at different levels is extracted through a novel dual multilevel graph neural network (DMGNN). We extensively validate the proposed method on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and experimental results demonstrate our method consistently outperforms other state-of-the-art multi-modal fusion methods. The code is publicly available on the GitHub website. (https://github.com/xiankantingqianxue/MIA-code.git).

6.
Small ; : e2403048, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708777

RESUMO

Silicon-based anodes heavily depend on the binder to preserve the unbroken electrode structure. In the present work, natural flaxseed gum (FG) is used as a binder of silicon nanoparticles (SiNPs) anode for the first time. Owing to a large number of polar groups and a rich branched structure, this material not only anchors tightly to the surface of SiNPs through bonding interactions but also formed a hydrogen bonding network structure among molecules. As a result, the FG binder can endow the silicon electrode with stable interfacial adhesion and outstanding mechanical properties. In addition, FG with a high viscosity facilitates the homogeneous dispersion of the electrode components. When FG is used as a binder, the cycling performance of the Si anode is greatly improved. After one hundred cycles at an applied current density of 1 A g-1, the electrode continues to display remarkable electrochemical properties with a significant cyclic capacity (2213 mA h g-1) and initial Coulombic efficiency (ICE) of 89.7%.

7.
Chem Sci ; 15(21): 8071-8079, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38817564

RESUMO

It is of great difficulty to create a new antimonite with second-harmonic-generation (SHG) intensity larger than 6 times that of KDP. In this study, a polyfluoroantimonite strategy has been proposed to explore fluoroantimonites with large nonlinear optical (NLO) coefficients. Under the cooperation of chemical (highly asymmetric π-conjugated organic amine) and physical (viscous reaction medium ethylene glycol) methods, two novel polyfluoroantimonites, namely, (3PC)2(Sb4F14) and (3AP)2(Sb4F13), have been achieved. Interestingly, these two structures contain two new polyfluoroantimonite groups respectively, an isolated (Sb4F14)2- four-member polyhedral ring and an infinite [Sb4F13]∞- helical chain. More importantly, the polar (3AP)2(Sb4F13) displays a strong SHG intensity of 8.1 × KDP, a large birefringence of 0.258@546 nm and a high laser-induced damage threshold (LIDT) value of 149.7 MW cm-2. Theoretical calculations indicated that its strong SHG effect stems from the synergistic effect of the helical [Sb4F13]∞- polyfluoroantimonite chain and π-conjugated 3AP+ cation, with a contribution ratio of 48.93% and 50.77% respectively. This work provides a new approach for the design and synthesis of high-performance fluoroantimonites.

8.
J Environ Sci (China) ; 143: 1-11, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38644008

RESUMO

Potential health risks related to environmental endocrine disruptors (EEDs) have aroused research hotspots at the forefront of water treatment technologies. Herein, nitrogen-doped titanium dioxide/schwertmannite nanocomposites (N-TiO2/SCH) have been successfully developed as heterogeneous catalysts for the degradation of typical EEDs via photo-Fenton processes. Due to the sustainable Fe(III)/Fe(II) conversion induced by photoelectrons, as-prepared N-TiO2/SCH nanocomposites exhibit much enhanced efficiency for the degradation of bisphenol A (BPA; ca. 100% within 60 min under visible irradiation) in a wide pH range of 3.0-7.8, which is significantly higher than that of the pristine schwertmannite (ca. 74.5%) or N-TiO2 (ca. 10.8%). In this photo-Fenton system, the efficient degradation of BPA is mainly attributed to the oxidation by hydroxyl radical (•OH) and singlet oxygen (1O2). Moreover, the possible catalytic mechanisms and reaction pathway of BPA degradation are systematically investigated based on analytical and photoelectrochemical analyses. This work not only provides a feasible means for the development of novel heterogeneous photo-Fenton catalysts, but also lays a theoretical foundation for the potential application of mineral-based materials in wastewater treatment.


Assuntos
Compostos Benzidrílicos , Compostos de Ferro , Nanocompostos , Nitrogênio , Fenóis , Titânio , Poluentes Químicos da Água , Titânio/química , Compostos Benzidrílicos/química , Fenóis/química , Nanocompostos/química , Poluentes Químicos da Água/química , Nitrogênio/química , Catálise , Ferro/química , Peróxido de Hidrogênio/química , Disruptores Endócrinos/química , Purificação da Água/métodos
9.
Biomed Chromatogr ; 38(6): e5866, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38618866

RESUMO

Immunoglobulin nephropathy (IgAN) stands as the most prevalent primary glomerular nephropathy globally, typically diagnosed through an invasive renal biopsy. Emerging research suggests the significant involvement of chiral amino acids in kidney disease progression. This study introduces a nonderivative LC-tandem mass spectrometry approach, offering efficient separation outcomes within 15 min for identifying chiral amino acids in human urine samples. Subsequently, using this method, the analysis of l- and d-amino acids in the urine of both patients with IgAN and healthy individuals was conducted. Fourteen d-amino acids and 20 l-amino acids were identified in the urine samples obtained from 17 patients with IgAN and 21 healthy individuals. The results indicated notable variances in the concentrations of both l- and d-amino acids between the IgAN and healthy control groups. In contrast to the healthy group, the IgAN group exhibited higher mean urine concentrations of most l-amino acids and lower concentrations of d-amino acids. Furthermore, correlations between amino acids and clinical markers were investigated. These results propose a novel method for monitoring trace amino acids in urine samples and introduce a new concept for potential markers of IgAN.


Assuntos
Aminoácidos , Glomerulonefrite por IGA , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Aminoácidos/urina , Glomerulonefrite por IGA/urina , Cromatografia Líquida/métodos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Biomarcadores/urina , Estereoisomerismo , Modelos Lineares , Estudos de Casos e Controles , Adulto Jovem
10.
J Colloid Interface Sci ; 667: 510-519, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38653072

RESUMO

Na super-ion conductor type material Na3V2(PO4)3 has been widely researched as the cathode of sodium-ion batteries (SIBs) in recent years, but the unsatisfying cost of Na3V2(PO4)3 impedes its wide application in SIBs. In this study, iron element is used to replace part of vanadium in Na3V2(PO4)3 to reduce its expense, and pine pollen is applied for the first time as a very effective carbon source to improve the performance of Na4FeV(PO4)3. The fabricated composite material achieves a capacity of 105 mA h g-1 under 0.2 C and fascinating cycling stability over 94 % under 2 C for 500 cycles and 98 % under 10 C for 1000 cycles. The excellent cycle performance is caused by the involvement of pine pollen that acts as a carbon matrix to enhance the electron conductivity and block the agglomeration of active material effectively, thus the well-dispersed nano sized Na4FeV(PO4)3 shortens the diffusion path of sodium ion and gains a remarkable rate capability. Moreover, the distinguished reversibility during the charge and discharge procedures is ascribed also to the robust structure of Na4FeV(PO4)3. This work provides an efficient route to realize the economic cathode material of SIBs with good performance.

11.
Exp Ther Med ; 27(4): 173, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476895

RESUMO

The dose-dependent pharmacological response to dapagliflozin in patients with type 2 diabetes mellitus (T2DM) with regard to weight loss remain unknown. The aim of the present study was to investigate the effects of dapagliflozin on weight loss in patients with T2DM. A total of 8,545 patients with T2DM from 24 randomized controlled trials reported in the literature were selected for inclusion in the study. Data from these trials were analyzed using maximal effect (Emax) models with nonlinear mixed effects modeling; the evaluation index was the body weight change rate from baseline values. Patients treated with 2.5 mg/day dapagliflozin exhibited an Emax of -3.04%, and the time taken for therapy to reach half of the Emax (ET50) was estimated to be 30.8 weeks for patients treated with this dose. Patients treated with 5, 10 and 20 mg/day dapagliflozin exhibited Emax values of -6.57, -4.12 and -3.23%, respectively, and their ET50 values were estimated to be 27.3, 20.4 and 4.23 weeks, respectively. The data indicated ideal linear relationships between individual predictions and observations, suggesting the optimal fitting of the final models. The present study is the first systematic analysis of the effect of dapagliflozin on weight loss in patients with T2DM. The application of dapagliflozin at 5 mg/day exhibited a greater weight loss effect compared with the other doses used, and the weight loss onset time shortened as the dose of dapagliflozin increased.

12.
J Am Chem Soc ; 146(11): 7868-7874, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38457655

RESUMO

Sulfate crystals are often criticized for their low birefringence. The small anisotropic SO4 group is becoming the biggest bottleneck hindering the application of sulfates in optical functional materials. In this study, we report a new method to significantly enhance the birefringence of sulfates. The title compound increases the birefringence recording of sulfates to 0.542@546 nm, which is significantly larger than that of the commercial birefringent crystal of TiO2 (0.306@546.1 nm). At the infrared wavelength, the birefringence of Hg4(Te2O5)(SO4) can be up to 0.400@1064 nm, which is also much larger than the infrared birefringent crystal of YVO4 (0.209@1064 nm). In addition, it also has a wide transparency range, high thermal stability, and excellent environmental stability, making it a potential birefringent material. Hg4(Te2O5)(SO4) features a novel two-dimensional layered structure composed of [Hg4(Te2O5)]2+ layers separated by isolated (SO4)2- tetrahedra. This compound was designed by introducing a highly selective cation in a tellurite sulfate system. The low valence low coordination cations connect with tellurite groups only, making the sulfate isolated in the structure. The steric repulsive action of the isolated SO4 tetrahedra may regulate the linear and lone pair groups arranged in a way that favors large birefringence. This method can be proven by theoretical calculations. PAWED studies showed that the large birefringence originated from the synergistic effect of (Hg2O2)2-, (Te2O5)2-, and (SO4)2- units, with a contribution ratio of 42.17, 37.92, and 19.88%, respectively. Our work breaks the limitation of low birefringence in sulfates and opens up new possibilities for their application as birefringent crystals.

13.
Inorg Chem ; 63(13): 6067-6074, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489513

RESUMO

The first examples of alkali metal selenite sulfates, namely, Na8(SeO3)(SO4)3 (1), Na2(H2SeO3)(SO4) (2), and K4(H2SeO3)(HSO4)2(SO4) (3), were successfully synthesized by hydrothermal reactions. Their structures display three different zero-dimensional configurations composed of isolated sulfate tetrahedra and selenite groups separated by alkali metals. Na8(SeO3)(SO4)3 (1) features a noncentrosymmetric structure, while Na2(H2SeO3)(SO4) (2) and K4(H2SeO3)(HSO4)2(SO4) (3) are centrosymmetric. Powder second-harmonic-generation measurements revealed that Na8(SeO3)(SO4)3 (1) shows a phase-matchable SHG intensity about 1.2 times that of KDP. UV-vis-NIR diffuse reflectance spectroscopic analysis indicated that Na8(SeO3)(SO4)3 (1) has a short UV cutoff edge and a large optical band gap, which makes it a possible UV nonlinear optical material. Theoretical calculations revealed that the birefringence of Na8(SeO3)(SO4)3 (1) is 0.041 at 532 nm, which is suitable for phase-matching condition. This work provides a good experimental foundation for the exploration of new UV nonlinear crystals in an alkali metal selenite sulfate system.

14.
Adv Healthc Mater ; 13(8): e2303101, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38174837

RESUMO

Ischemia-induced myocardial injury has become a serious threat to human health, and its treatment remains a challenge. The occurrence of ischemic events leads to a burst release of reactive oxygen species (ROS), which triggers extensive oxidative damage and leads to dysfunctional autophagy, making it difficult for cells to maintain homeostasis. Antioxidants and modulation of autophagy have thus become promising strategies for the treatment of ischemic myocardial injury. This study proposes an antioxidant-activated autophagy therapeutic regimen based on combining melanin (Mel), an excellent antioxidant with metformin mimetic ploymetformin via electrostatic interactions, to obtain a nanocomplex (Met-Mel). The nanocomplex is finally encapsulated with platelet membranes (PMN) to construct a biomimetic nanoparticle (PMN@Met-Mel) capable of targeting injured myocardium. The prepared PMN@Met-Mel has good Mel loading capacity and optimal biosafety. It exhibits excellent antioxidant activity and autophagy activation, rapidly restoring mitochondrial function. Moreover, RNA sequencing (RNA-seq) analysis reveals that PMN@Met-Mel operates mechanistically by triggering the activation of the autophagy pathway. Subsequent in vivo experiments showcase promising cardioprotective effects of these nanoparticles. These discoveries present a newly devised nanoplatform with promising potential for the effective treatment of myocardial infarction.


Assuntos
Antioxidantes , Infarto do Miocárdio , Humanos , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo
15.
Cell Mol Life Sci ; 81(1): 23, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38200266

RESUMO

The functional and structural changes in the proximal tubule play an important role in the occurrence and development of diabetic kidney disease (DKD). Diabetes-induced metabolic changes, including lipid metabolism reprogramming, are reported to lead to changes in the state of tubular epithelial cells (TECs), and among all the disturbances in metabolism, mitochondria serve as central regulators. Mitochondrial dysfunction, accompanied by increased production of mitochondrial reactive oxygen species (mtROS), is considered one of the primary factors causing diabetic tubular injury. Most studies have discussed how altered metabolic flux drives mitochondrial oxidative stress during DKD. In the present study, we focused on targeting mitochondrial damage as an upstream factor in metabolic abnormalities under diabetic conditions in TECs. Using SS31, a tetrapeptide that protects the mitochondrial cristae structure, we demonstrated that mitochondrial oxidative damage contributes to TEC injury and lipid peroxidation caused by lipid accumulation. Mitochondria protected using SS31 significantly reversed the decreased expression of key enzymes and regulators of fatty acid oxidation (FAO), but had no obvious effect on major glucose metabolic rate-limiting enzymes. Mitochondrial oxidative stress facilitated renal Sphingosine-1-phosphate (S1P) deposition and SS31 limited the elevated Acer1, S1pr1 and SPHK1 activity, and the decreased Spns2 expression. These data suggest a role of mitochondrial oxidative damage in unbalanced lipid metabolism, including lipid droplet (LD) formulation, lipid peroxidation, and impaired FAO and sphingolipid homeostasis in DKD. An in vitro study demonstrated that high glucose drove elevated expression of cytosolic phospholipase A2 (cPLA2), which, in turn, was responsible for the altered lipid metabolism, including LD generation and S1P accumulation, in HK-2 cells. A mitochondria-targeted antioxidant inhibited the activation of cPLA2f isoforms. Taken together, these findings identify mechanistic links between mitochondrial oxidative metabolism and reprogrammed lipid metabolism in diabetic TECs, and provide further evidence for the nephroprotective effects of SS31 via influencing metabolic pathways.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Metabolismo dos Lipídeos , Mitocôndrias , Estresse Oxidativo , Células Epiteliais , Glucose , Lipídeos
16.
Cyborg Bionic Syst ; 5: 0062, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188984

RESUMO

Tumors significantly impact individuals' physical well-being and quality of life. With the ongoing advancements in optical technology, information technology, robotic technology, etc., laser technology is being increasingly utilized in the field of tumor treatment, and laser ablation (LA) of tumors remains a prominent area of research interest. This paper presents an overview of the recent progress in tumor LA therapy, with a focus on the mechanisms and biological effects of LA, commonly used ablation lasers, image-guided LA, and robotic-assisted LA. Further insights and future prospects are discussed in relation to these aspects, and the paper proposed potential future directions for the development of tumor LA techniques.

17.
Dalton Trans ; 53(4): 1663-1672, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38168800

RESUMO

The electrocatalytic mechanisms of CO2 reduction catalyzed by pyridine-oxazoline (pyrox)-based Mn catalysts were investigated by DFT calculations. In-depth comparative analyses of pyrox-based and bipyridine-based Mn complexes were carried out. C-OH cleavage is the rate-determining step for both the protonation-first path and the reduction-first path. The free energy of CO2 activation (ΔG1) and the electrons donated by CO ligands in this step are effective descriptors in regulating the C-OH cleavage barrier. The reduction of carboxylate complex 6 (E6) is the potential-determining step for the reduction-first path. Meanwhile, for the protonation-first path, the initial generation (E2) or the regeneration (E8) of active catalyst might be potential-determining. Hirshfeld charge and orbital contribution analysis indicate that E6 is definitely based on the heterocyclic ligand and E2 is related to both the heterocyclic ligand and three CO ligands. Therefore, replacement of the CO ligand by a stronger electron donating ligand can effectively boost the catalytic activity of CO2 reduction without increasing the overpotential in the reduction-first path. This hypothesis is supported by the mechanism calculations of the Mn complex in which the axial CO ligand is replaced by a pyridine or PMe3.

18.
Heliyon ; 10(2): e24340, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293540

RESUMO

In recent years, glucagon-like peptide-1 (GLP-1) has demonstrated considerable potential in the treatment of type 2 diabetes (T2D) and obesity. However, the half-life of naturally occurring GLP-1 is quite short in vivo. Two common strategies employed for half-life extension are the use of the Albumin-binding domain (ABD) and XTEN polypeptide, which operate through different mechanisms. In this study, we designed an innovative GLP-1 receptor agonist with an extended duration of action. This new construct incorporated an albumin binding domain (ABD) and an XTEN sequence (either XTEN144 or XTEN288) as carriers. We referred to these fusion proteins as GLP-ABD-XTEN144 and GLP-ABD-XTEN288. In an E. coli system, the said constructs were efficaciously produced in substantial quantity. It was observed from in vitro studies that the fusion protein GLP-ABD-XTEN144 demonstrated a five times stronger affinity towards human serum albumin (HSA), boasting a binding affinity (Kd) of 5.50 nM. This was in contrast to GLP-ABD-XTEN288, whose Kd value was registered at 27.78 nM. Moreover, GLP-ABD-XTEN144 presented a half-life of 12.9 h in mice, thus exceeding the corresponding value for GLP-ABD-XTEN288, 7.32 h in mice. Both these fusion proteins significantly mitigated non-fasting blood sugar levels and overall food consumption for 48 h subsequent to a one-time injection in mice. Notably, GLP-ABD-XTEN144 exhibited more pronounced hypoglycemic activity and food inhibitory effects than GLP-ABD-XTEN288. The designed GLP-ABD-XTEN144 fusion protein shows promising prospects for clinical application in T2D treatment. Our findings also suggest that ABD and XTEN polypeptides synergistically contribute to half-life extension, further enhancing the pharmacokinetic characteristics of a payload.

19.
Proc Inst Mech Eng H ; 238(2): 207-218, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38235731

RESUMO

A finite element model with realistic bone geometries is developed to design optimal internal fixation during the fibula healing process in this study. The effect of bone plate parameters on fibula fracture healing is studied. The relationship between differences in plate length, thickness and working length, and bone healing performance is focused. The optimal combination form of the bone plate parameters was selected by the orthogonal experimental design and fracture block strain to achieve bone healing maximize the performance. The model results show that the maximum equivalent force of the bone plate was below the material yield limit; the higher mean contact stresses in the bone fragments indicate that the bone plate is prone to higher contact stresses when they are long. The working length of the bone plate has a greater effect on callus healing than the thickness and length of the bone plate. The optimal internal fixation option for distal fibula fractures is achieved when it provides the stability required for internal fixation during bone healing. It ensures lower contact stresses in the fibula as well as maximum Young's modulus during callus healing process.


Assuntos
Fíbula , Fixação Interna de Fraturas , Fíbula/cirurgia , Análise de Elementos Finitos , Placas Ósseas , Consolidação da Fratura , Fenômenos Biomecânicos
20.
Cells ; 12(23)2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38067181

RESUMO

Automated evaluation of all glomeruli throughout the whole kidney is essential for the comprehensive study of kidney function as well as understanding the mechanisms of kidney disease and development. The emerging large-volume microscopic optical imaging techniques allow for the acquisition of mouse whole-kidney 3D datasets at a high resolution. However, fast and accurate analysis of massive imaging data remains a challenge. Here, we propose a deep learning-based segmentation method called FastCellpose to efficiently segment all glomeruli in whole mouse kidneys. Our framework is based on Cellpose, with comprehensive optimization in network architecture and the mask reconstruction process. By means of visual and quantitative analysis, we demonstrate that FastCellpose can achieve superior segmentation performance compared to other state-of-the-art cellular segmentation methods, and the processing speed was 12-fold higher than before. Based on this high-performance framework, we quantitatively analyzed the development changes of mouse glomeruli from birth to maturity, which is promising in terms of providing new insights for research on kidney development and function.


Assuntos
Aprendizado Profundo , Animais , Camundongos , Rim/diagnóstico por imagem , Glomérulos Renais/diagnóstico por imagem , Imagem Óptica
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