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1.
Food Chem ; 460(Pt 2): 140635, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39111140

RESUMEN

The objective of this study was to identify bioactive oligosaccharides and peptides in the cooking water of chickpeas and common beans, known as aquafaba. The oligosaccharides stachyose, raffinose and verbascose were quantified by high-performance anion-exchange chromatography; 78 and 67 additional oligosaccharides were identified in chickpea and common bean aquafaba, respectively, by LC-MS/MS. Chickpea aquafaba uniquely harbored ciceritol and other methyl-inositol-containing oligosaccharides. In prebiotic growth assays, chickpea aquafaba oligosaccharides were differentially utilized, promoting growth of Limosilactobacillus reuteri DSM 20016 and Bifidobacterium longum subsp. infantis ATCC 15697, but not Lacticaseibacillus rhamnosus GG. Dimethyl labeling, along with LC-MS/MS, effectively differentiated α- and γ-glutamyl peptides, revealing the presence of several γ-glutamyl peptides known to possess kokumi and anti-inflammatory activities, including γ-Glu-Phe and γ-Glu-Tyr in chickpeas aquafaba and γ-Glu-S-methyl-Cys and γ-Glu-Leu in beans aquafaba. This work uncovered unique bioactive peptides and oligosaccharides in aquafaba, helping promote its valorization, food system sustainability, and future health-promoting claims.

2.
Mol Breed ; 44(8): 52, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39130615

RESUMEN

The anthocyanin accumulation in juvenile tissues can enhance the ornamental value, attract pollinators, and help improve abiotic stress. Although transcriptional regulation studies of anthocyanin have been relatively extensive, there are few reports on the mechanism of anthocyanin accumulation in young tissues. This study reveals that many juvenile citrus tissues (flowers, leaves, and pericarp) undergo transient accumulation of anthocyanins, exhibiting a red coloration. Using weighted gene co-expression network analysis (WGCNA) identified CitWRKY75 as a candidate gene. After detecting the expression levels of CitWRKY75 in various citrus juvenile tissues, the expression trend of CitWRKY75 was highly consistent with the red exhibiting and fading. Overexpression of CitWRKY75 in tobacco significantly increased the anthocyanin content. LUC and yeast one-hybrid assay demonstrated that CitWRKY75 could bind to the promoter of CitRuby1(encoding the key transcription factor promoting anthocyanin accumulation) and promote its expression. Finally, comparing the expression levels of CitWRKY75 and CitRuby1 in the late development stage of blood orange found that CitWRKY75 was not the main regulatory factor for anthocyanin accumulation in the later stage. This study used reverse genetics to identify a transcription factor, CitWRKY75, upstream of CitRuby1, which promotes anthocyanin accumulation in citrus juvenile tissues. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01490-9.

3.
J Biomed Opt ; 29(7): 076003, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38989529

RESUMEN

Significance: Tissues' biomechanical properties, such as elasticity, are related to tissue health. Optical coherence elastography produces images of tissues based on their elasticity, but its performance is constrained by the laser power used, working distance, and excitation methods. Aim: We develop a new method to reconstruct the elasticity contrast image over a long working distance, with only low-intensity illumination, and by non-contact acoustic wave excitation. Approach: We combine single-photon vibrometry and quantum parametric mode sorting (QPMS) to measure the oscillating backscattered signals at a single-photon level and derive the phantoms' relative elasticity. Results: We test our system on tissue-mimicking phantoms consisting of contrast sections with different concentrations and thus stiffness. Our results show that as the driving acoustic frequency is swept, the phantoms' vibrational responses are mapped onto the photon-counting histograms from which their mechanical properties-including elasticity-can be derived. Through lateral and longitudinal laser scanning at a fixed frequency, a contrast image based on samples' elasticity can be reliably reconstructed upon photon level signals. Conclusions: We demonstrated the reliability of QPMS-based elasticity contrast imaging of agar phantoms in a long working distance, low-intensity environment. This technique has the potential for in-depth images of real biological tissue and provides a new approach to elastography research and applications.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Fantasmas de Imagen , Fotones , Diagnóstico por Imagen de Elasticidad/métodos , Diagnóstico por Imagen de Elasticidad/instrumentación , Procesamiento de Imagen Asistido por Computador/métodos , Elasticidad , Reproducibilidad de los Resultados
4.
Opt Express ; 32(10): 16657-16669, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858866

RESUMEN

We demonstrate a single-photon counting Raman spectroscope and benchmark it against conventional and surface-enhanced Raman spectroscopy. For direct comparison without ambiguity, we use the same solutions of Rhodamine 6G and a common optical setup with either a spectrometer or an acousto-optic tunable filter, whereas the surface enhancement is realized with immobilized Ag nanoparticles. Our results find that the single photon counting significantly elevates the detection sensitivity by up to eight orders of magnitude, arriving at a comparable level of surface-enhanced Raman spectroscopy. Another significant advantage is with the time-resolving measurement, where we demonstrate time-gated and time-correlated single-photon counting with sub-nanosecond resolution. It offers insights into the samples' transient responses and enables the isolation of Raman scattering from fluorescence signals.

5.
Opt Lett ; 49(12): 3388-3391, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38875627

RESUMEN

We demonstrate an invertible all-optical gate on chip, with the roles of control and signal switchable by slightly adjusting their relative arrival time at the gate. It is based on the quantum Zeno blockade (QZB) driven by sum-frequency generation (SFG) in a periodically poled lithium niobate microring resonator. For two nearly identical nanosecond pulses, the later arriving pulse is modulated by the earlier arriving one, resulting in 2.4 and 3.9 power extinction between the two, respectively, when their peak powers are 1 mW and 2 mW, respectively. Our results, while to be improved and enriched, herald a new, to the best of our knowledge, paradigm of logical gates and circuits for exotic applications.

6.
Nat Food ; 5(6): 480-490, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38872016

RESUMEN

Human milk oligosaccharides (HMOs) are a diverse class of carbohydrates which support the health and development of infants. The vast health benefits of HMOs have made them a commercial target for microbial production; however, producing the approximately 200 structurally diverse HMOs at scale has proved difficult. Here we produce a diversity of HMOs by leveraging the robust carbohydrate anabolism of plants. This diversity includes high-value and complex HMOs, such as lacto-N-fucopentaose I. HMOs produced in transgenic plants provided strong bifidogenic properties, indicating their ability to serve as a prebiotic supplement with potential applications in adult and infant health. Technoeconomic analyses demonstrate that producing HMOs in plants provides a path to the large-scale production of specific HMOs at lower prices than microbial production platforms. Our work demonstrates the promise in leveraging plants for the low-cost and sustainable production of HMOs.


Asunto(s)
Leche Humana , Oligosacáridos , Plantas Modificadas Genéticamente , Oligosacáridos/metabolismo , Humanos , Leche Humana/metabolismo , Leche Humana/química , Plantas Modificadas Genéticamente/genética , Prebióticos , Fotosíntesis
7.
Opt Lett ; 49(9): 2449-2452, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691741

RESUMEN

Broadband frequency comb generation through cascaded quadratic nonlinearity remains experimentally untapped in free-space cavities with bulk χ(2) materials mainly due to the high threshold power and restricted ability of dispersion engineering. Thin-film lithium niobate (LN) is a good platform for nonlinear optics due to the tight mode confinement in a nano-dimensional waveguide, the ease of dispersion engineering, large quadratic nonlinearities, and flexible phase matching via periodic poling. Here we demonstrate broadband frequency comb generation through dispersion engineering in a thin-film LN microresonator. Bandwidths of 150 nm (80 nm) and 25 nm (12 nm) for center wavelengths at 1560 and 780 nm are achieved, respectively, in a cavity-enhanced second-harmonic generation (doubly resonant optical parametric oscillator). Our demonstration paves the way for pure quadratic soliton generation, which is a great complement to dissipative Kerr soliton frequency combs for extended interesting nonlinear applications.

8.
Crit Rev Biotechnol ; : 1-17, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710624

RESUMEN

Constipation is a common gastrointestinal condition, which may occur at any age and affects countless people. The search for new treatments for constipation is ongoing as current drug treatments fail to provide fully satisfactory results. In recent years, probiotics have attracted much attention because of their demonstrated therapeutic efficacy and fewer side effects than pharmaceutical products. Many studies attempted to answer the question of how probiotics can alleviate constipation. It has been shown that different probiotic strains can alleviate constipation by different mechanisms. The mechanisms on probiotics in relieving constipation were associated with various aspects, including regulation of the gut microbiota composition, the level of short-chain fatty acids, aquaporin expression levels, neurotransmitters and hormone levels, inflammation, the intestinal environmental metabolic status, neurotrophic factor levels and the body's antioxidant levels. This paper summarizes the perception of the mechanisms on probiotics in relieving constipation and provides some suggestions on new research directions.

9.
Medicine (Baltimore) ; 103(21): e37388, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38788037

RESUMEN

To investigate the effects and molecular mechanisms of wedelolactone (WEL) on high glucose-induced injury of human retinal vascular endothelial cells (HRECs). The cell injury model was established by incubating HRECs with 30 mmol/L glucose for 24 hour. HRECs were divided into control (Con) group, high glucose (HG) group, HG + WEL-low dose (L) group, HG + WEL-medium dose (M), HG + WEL-high dose (H) group, HG + miR-NC group, HG + miR-190 group, HG + WEL + antimiR-NC group, HG + WEL + antimiR-190 group. The kit detects cellular reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) content; cell apoptosis was analyzed by flow cytometry; miR-190 expression was detected by real-time quantitative PCR (RT-qPCR). Compared with Con group, the levels of ROS and MDA in the HG group were significantly increased (P < .01), the SOD activity and the expression of miR-190 expression were significantly decreased (P < .05), and the apoptosis rate was significantly increased (P < .01). Compared with HG group, the levels of ROS and MDA in HG + WEL-L group, HG + WEL-M group and HG + WEL-H group were significantly decreased (P < .05), SOD activity and miR-190 expression were significantly increased (P < .05), and apoptosis rate was significantly reduced (P < .05). Compared with the HG + miR-NC group, the levels of ROS and MDA in HG + miR-190 group were significantly reduced (P < .01), SOD activity was significantly increased (P < .01), and apoptosis rate was significantly reduced (P < .05). Compared with the HG + WEL + antimiR-NC group, the ROS level and MDA content in the HG + WEL + antimiR-190 group were significantly increased (P < .05), SOD activity was significantly decreased (P < .05), and apoptosis rate was significantly increased (P < .05). Wedelolactone can attenuate high glucose-induced HRECs apoptosis and oxidative stress by up-regulating miR-190 expression.


Asunto(s)
Apoptosis , Cumarinas , Células Endoteliales , Glucosa , MicroARNs , Especies Reactivas de Oxígeno , Humanos , MicroARNs/metabolismo , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Cumarinas/farmacología , Superóxido Dismutasa/metabolismo , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/metabolismo , Células Cultivadas
10.
J Nanobiotechnology ; 22(1): 256, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755613

RESUMEN

BACKGROUND: Gastric cancer represents a highly lethal malignancy with an elevated mortality rate among cancer patients, coupled with a suboptimal postoperative survival prognosis. Nectin-4, an overexpressed oncological target for various cancers, has been exploited to create antibody-drug conjugates (ADCs) to treat solid tumors. However, there is limited research on Nectin-4 ADCs specifically for gastric cancer, and conventional immunoglobulin G (IgG)-based ADCs frequently encounter binding site barriers. Based on the excellent tumor penetration capabilities inherent in nanobodies (Nbs), we developed Nectin-4-targeting Nb drug conjugates (NDCs) for the treatment of gastric cancer. RESULTS: An immunized phage display library was established and employed for the selection of Nectin-4-specific Nbs using phage display technology. Subsequently, these Nbs were engineered into homodimers to enhance Nb affinity. To prolong in vivo half-life and reduce immunogenicity, we fused an Nb targeting human serum albumin (HSA), resulting in the development of trivalent humanized Nbs. Further, we site-specifically conjugated a monomethyl auristatin E (MMAE) at the C-terminus of the trivalent Nbs, creating Nectin-4 NDC (huNb26/Nb26-Nbh-MMAE) with a drug-to-antibody ratio (DAR) of 1. Nectin-4 NDC demonstrated excellent in vitro cell-binding activities and cytotoxic efficacy against cells with high Nectin-4 expression. Subsequent administration of Nectin-4 NDC to mice bearing NCI-N87 human gastric cancer xenografts demonstrated rapid tissue penetration and high tumor uptake through in vivo imaging. Moreover, Nectin-4 NDC exhibited noteworthy dose-dependent anti-tumor efficacy in in vivo studies. CONCLUSION: We have engineered a Nectin-4 NDC with elevated affinity and effective tumor uptake, further establishing its potential as a therapeutic agent for gastric cancer.


Asunto(s)
Antineoplásicos , Moléculas de Adhesión Celular , Inmunoconjugados , Ratones Desnudos , Anticuerpos de Dominio Único , Neoplasias Gástricas , Neoplasias Gástricas/tratamiento farmacológico , Humanos , Animales , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/farmacología , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Ratones , Inmunoconjugados/química , Inmunoconjugados/farmacología , Inmunoconjugados/farmacocinética , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Endogámicos BALB C , Femenino , Ensayos Antitumor por Modelo de Xenoinjerto , Oligopéptidos/química , Oligopéptidos/farmacología , Nectinas
11.
Comput Biol Med ; 173: 108381, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38569237

RESUMEN

Multimodal medical image fusion (MMIF) technology plays a crucial role in medical diagnosis and treatment by integrating different images to obtain fusion images with comprehensive information. Deep learning-based fusion methods have demonstrated superior performance, but some of them still encounter challenges such as imbalanced retention of color and texture information and low fusion efficiency. To alleviate the above issues, this paper presents a real-time MMIF method, called a lightweight residual fusion network. First, a feature extraction framework with three branches is designed. Two independent branches are used to fully extract brightness and texture information. The fusion branch enables different modal information to be interactively fused at a shallow level, thereby better retaining brightness and texture information. Furthermore, a lightweight residual unit is designed to replace the conventional residual convolution in the model, thereby improving the fusion efficiency and reducing the overall model size by approximately 5 times. Finally, considering that the high-frequency image decomposed by the wavelet transform contains abundant edge and texture information, an adaptive strategy is proposed for assigning weights to the loss function based on the information content in the high-frequency image. This strategy effectively guides the model toward preserving intricate details. The experimental results on MRI and functional images demonstrate that the proposed method exhibits superior fusion performance and efficiency compared to alternative approaches. The code of LRFNet is available at https://github.com/HeDan-11/LRFNet.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Análisis de Ondículas
12.
Sci Rep ; 14(1): 3473, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347077

RESUMEN

High-power inductors are fundamental components in high-power DC-DC converters, with their performance being a crucial metric of converter efficiency. This paper presents an in-depth analysis of a novel calculation method for the air gap length in such inductors. Taking into account the effects of air gap diffusion and the winding magnetic field, an expression for the air gap diffusion radius is derived, focusing on a distributed air gap structure. Furthermore, models for calculating the air gap and winding reluctance are developed, grounded in electromagnetic field theory. An equivalent magnetic circuit model, formulated based on Kirchhoff's second law, facilitates the proposed method for air gap length calculation. This study also involves the development of 3D models for both discrete and decoupled integrated inductors. The comparison between simulation outcomes and calculated air gap lengths indicates a maximum error of less than 8%, with the minimum error being as low as - 0.79%. Compared with traditional methods, the calculation method proposed in this paper has significant advantages. Additionally, the discrepancy between calculated values and experimental measurements is found to be 1.11%. These results validate the accuracy and applicability of the theoretical analysis and calculation method, underscoring their significance in the design and optimization of high-power DC-DC converters.

13.
Environ Sci Pollut Res Int ; 31(10): 15209-15222, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38289558

RESUMEN

Utilizing cost-effective corn cob, zinc chloride-modified biochar was synthesized through one-step method for benzene adsorption from air. Study on impregnation ratio impact showed optimal benzene adsorption at ZnCl2:CC ratio of 1.5:1, with capacity reaching 170.53 mg g-1. Characterization using BET, SEM, FTIR, and XPS was conducted. BET results indicated specific surface area of Zn1.5BC at 1260.63 m2 g-1 and maximum pore volume of 0.546 m3 g-1. SEM analysis revealed microporous-mesoporous structure in Zn1.5BC, marking significant improvement over original biomass. DFT pore size distribution and FTIR analysis suggested post-modification dehydration and elimination reactions, leading to volatile compound release, functional group reduction, and pore widening. XPS analysis showed decrease in O = C-OH content with increased impregnation ratio, enhancing biochar's π-π electron diffusion for benzene. Langmuir isotherm and pseudo-second-order kinetic models effectively described experimental data, indicating multilayer benzene adsorption on biochar controlled by complex physicochemical adsorption and pore diffusion. Adsorption condition assessment, including adsorption temperature (20-120 â„ƒ) and benzene concentration in inlet phase (159.73-383.36 mg L-1), was performed. Yoon-Nelson model fitting indicated adsorption site loss at higher temperatures and reduced capture ability due to increased adsorbate molecule kinetic energy. Higher adsorbate concentrations aided adsorption molecule diffusion to biochar surface and internal pores, increasing adsorption rate and shortening equilibrium time. Overall, zinc chloride-modified biochar facilitates benzene adsorption through pore filling and π-π interactions, with pore filling as primary mechanism. Produced biochar shows excellent regeneration properties and reusability.


Asunto(s)
Benceno , Cloruros , Contaminantes Químicos del Agua , Compuestos de Zinc , Zea mays , Adsorción , Contaminantes Químicos del Agua/química , Carbón Orgánico/química , Cinética
14.
Genes Dis ; 11(3): 100986, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38292181

RESUMEN

Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological, cellular, and clinical levels. Rheumatologists have marked them as two entirely distinct arthropathies. Given recent discoveries in disease initiation and progression, potential mechanisms, cellular signaling pathways, and ongoing clinical therapeutics, there are now more opportunities for discovering osteoarthritis drugs. This review summarized the osteoarthritis and psoriasis arthritis signaling pathways, crosstalk between BMP, WNT, TGF-ß, VEGF, TLR, and FGF signaling pathways, biomarkers, and anatomical pathologies. Through bench research, we demonstrated that regenerative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses, multiple signaling blockers, and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation. Furthermore, we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.

15.
Small Methods ; 8(3): e2300793, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38009512

RESUMEN

The high-efficient and low-cost oxygen evolution reaction (OER) is decisive for applications of oxide catalysts in metal-air batteries, electrolytic cells, and energy-storage technologies. Delicate regulations of active surface and catalytic reaction pathway of oxide materials principally determine thermodynamic energy barrier and kinetic rate during catalytic reactions, and thus have crucial impacts on OER performance. Herein, a synergistic modulation of catalytically active surface and reaction pathway through facile topotactic transformations switching from perovskite (PV) LaNiO3.0 film to infinite-layer (IL) LaNiO2.0 film is demonstrated, which absolutely contributes to improving OER performance. The square-planar NiO4 coordination of IL-LaNiO2.0 brings about more electrochemically active metal (Ni+ ) sites on the film surface. Meanwhile, the oxygen-deficient driven PV- IL topotactic transformations lead to a reaction pathway converted from absorbate evolution mechanism to lattice-oxygen-mediated mechanism (LOM). The non-concerted proton-electron transfer of LOM pathway, evidenced by the pH-dependent OER kinetics, further boosts the OER activity of IL-LaNiO2.0 films. These findings will advance the in-depth understanding of catalytic mechanisms and open new possibilities for developing highly active perovskite-derived oxide catalysts.

16.
J Pediatr Nurs ; 75: 99-107, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38134732

RESUMEN

PURPOSE: To explore the lived experiences of the caregivers of children with developmental delay (DD) on the remote island of Kinmen, Taiwan. DESIGN AND METHODS: This descriptive phenomenological study included 14 caregivers of 16 children with DD recruited from Kinmen, Taiwan. Data were collected from September 2020 to February 2021 with face-to-face semi-structured interviews, which were transcribed verbatim and analyzed using thematic analysis. RESULTS: Twelve caregivers were mothers; there was one father and one grandmother. Their mean age was 37.93 ± 5.17 years. The mean age of the children was 3.90 ± 1.49 years; 11 were male (69%). As we began our study, the COVID-19 pandemic occurred, which influenced two of the three themes: (1) focusing on their child's delayed development, which involved seeking a diagnosis and blaming themselves; (2) facing barriers to caring a child with DD on a remote island, which included ostracization of their child and limited off-island medical resources, especially during COVID-19; and (3) maintaining a healthy life balance, which involved protecting their child from physical or spiritual harm, including exposure to COVID-19, and reflecting on their strengths. CONCLUSIONS: Our findings highlight the challenges of caring for a child with DD in the Kinmen islands of Taiwan, and the impact of the COVID-19 pandemic. PRACTICAL IMPLICATIONS: Healthcare professionals are encouraged to provide caregivers of children with DD living in remote, island communities an opportunity to share their caregiving experiences and provide strategies for obtaining medical care, which could help reduce caregiver burden.


Asunto(s)
COVID-19 , Cuidadores , Niño , Femenino , Humanos , Masculino , Adulto , Preescolar , Estrés Psicológico , Pandemias , Madres , COVID-19/epidemiología , Investigación Cualitativa
17.
Nanomaterials (Basel) ; 13(24)2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38132996

RESUMEN

The detection and feedback of displacement and velocity significantly impact the control accuracy of the linear feed system. In this study, we propose a flexible and self-powered displacement sensor based on the triboelectric effect, designed for seamless integration into linear feed systems. The displacement sensor comprises two parts, the mover and stator, operating in a sliding mode. This sensor can precisely detect the displacement of the linear feed system with a large detection range. Additionally, the sensor is capable of real-time velocity detection of linear feed systems, with an error rate below 0.5%. It also offers advantages, such as excellent flexibility, compact size, stability, easy fabrication, and seamless integration, with linear feed systems. These results highlight the potential of the self-powered displacement sensor for various applications in linear feed systems.

18.
J Nanobiotechnology ; 21(1): 410, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37932752

RESUMEN

BACKGROUND: Pancreatic cancer is a highly aggressive malignancy with limited treatment options and a poor prognosis. Trophoblast cell surface antigen 2 (TROP2), a cell surface antigen overexpressed in the tumors of more than half of pancreatic cancer patients, has been identified as a potential target for antibody-drug conjugates (ADCs). Almost all reported TROP2-targeted ADCs are of the IgG type and have been poorly studied in pancreatic cancer. Here, we aimed to develop a novel nanobody-drug conjugate (NDC) targeting TROP2 for the treatment of pancreatic cancer. RESULTS: In this study, we developed a novel TROP2-targeted NDC, HuNbTROP2-HSA-MMAE, for the treatment of TROP2-positive pancreatic cancer. HuNbTROP2-HSA-MMAE is characterized by the use of nanobodies against TROP2 and human serum albumin (HSA) and has a drug-antibody ratio of 1. HuNbTROP2-HSA-MMAE exhibited specific binding to TROP2 and was internalized into tumor cells with high endocytosis efficiency within 5 h, followed by intracellular translocation to lysosomes and release of MMAE to induce cell apoptosis in TROP2-positive pancreatic cancer cells through the caspase-3/9 pathway. In a xenograft model of pancreatic cancer, doses of 0.2 mg/kg and 1 mg/kg HuNbTROP2-HSA-MMAE demonstrated significant antitumor effects, and a dose of 5 mg/kg even eradicated the tumor. CONCLUSION: HuNbTROP2-HSA-MMAE has desirable affinity, internalization efficiency and antitumor activity. It holds significant promise as a potential therapeutic option for the treatment of TROP2-positive pancreatic cancer.


Asunto(s)
Inmunoconjugados , Neoplasias Pancreáticas , Humanos , Antígenos de Superficie , Línea Celular Tumoral , Inmunoconjugados/química , Neoplasias Pancreáticas/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Neoplasias Pancreáticas
19.
Ecotoxicol Environ Saf ; 267: 115666, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37944465

RESUMEN

BACKGROUND: Exposure to inhalable environmental particulate matter with a diameter of 2.5 µm or smaller (PM2.5) is associated with decreased or impaired kidney function, but the underlying biological mechanisms are not fully understood. Gut microbiota is an emerging key player in the homeostasis regulation of the gut-kidney axis. Few studies have investigated its role in PM2.5 exposure-induced gut-kidney axis homeostasis abnormalities. METHODS: In this study, a versatile aerosol concentration enrichment system for medium- to long-term whole-body exposure was used to expose Sprague-Dawley rats to filtered air (FA) or concentrated ambient PM2.5 for 12 weeks. A correlation analysis of renal impairment and the intestinal microbiome was performed. RESULTS: The urine flow rate calculation and renal function analysis showed that PM2.5 exposure significantly impaired renal function and increased the urine flow rate. The fecal microbiota analysis showed that renal impairment and increased urine flow rates were consistent with the reduced estimates of the fecal bacteria Chao1, observed-species, Shannon, and Simpson (richness and diversity indices). Pearson's correlation analysis showed that the estimated bacterial richness and diversity were correlated with the urine flow rate and renal function. The linear discriminant analysis effect size (LEfSe) analysis revealed differences between animals exposed to PM2.5 and FA in 25 bacterial groups. Further correlation of a single bacterial taxon with the urine flow rate and renal function showed that the relative abundances of 30, 29, 21, and 50 distinct bacterial groups were significantly correlated with the urine flow rate, estimated glomerular filtration rate (eGFR), serum cystatin C (CysC), and beta-2 microglobulin (ß2-MG), respectively. CONCLUSION: Subchronic exposure to PM2.5 can cause intestinal ecological disorders, which may, in turn, lead to decreased kidney function or the development of impaired kidney function.


Asunto(s)
Contaminantes Atmosféricos , Microbioma Gastrointestinal , Ratas , Animales , Ratas Sprague-Dawley , Material Particulado/toxicidad , Material Particulado/análisis , Riñón/fisiología , Riñón/química , Tasa de Filtración Glomerular , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis
20.
bioRxiv ; 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37786679

RESUMEN

Human milk oligosaccharides (HMOs) are a diverse class of carbohydrates that aid in the health and development of infants. The vast health benefits of HMOs have made them a commercial target for microbial production; however, producing the ∼130 structurally diverse HMOs at scale has proven difficult. Here, we produce a vast diversity of HMOs by leveraging the robust carbohydrate anabolism of plants. This diversity includes high value HMOs, such as lacto-N-fucopentaose I, that have not yet been commercially produced using state-of-the-art microbial fermentative processes. HMOs produced in transgenic plants provided strong bifidogenic properties, indicating their ability to serve as a prebiotic supplement. Technoeconomic analyses demonstrate that producing HMOs in plants provides a path to the large-scale production of specific HMOs at lower prices than microbial production platforms. Our work demonstrates the promise in leveraging plants for the cheap and sustainable production of HMOs.

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