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1.
Artigo em Inglês | MEDLINE | ID: mdl-38957995

RESUMO

Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.

2.
Stem Cell Rev Rep ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951308

RESUMO

Mutations in STAMBP have been well-established to cause congenital human microcephaly-capillary malformation (MIC-CAP) syndrome, a rare genetic disorder characterized by global developmental delay, severe microcephaly, capillary malformations, etc. Previous biochemical investigations and loss-of-function studies in mice have provided insights into the mechanism of STAMBP, however, it remains controversial how STAMBP deficiency leads to malformation of those affected tissues in patients. In this study, we investigated the function and underlying mechanism of STAMBP during neural differentiation of human embryonic stem cells (hESCs). We found that STAMBP is dispensable for the pluripotency maintenance or neural differentiation of hESCs. However, neural progenitor cells (NPCs) derived from STAMBP-deficient hESCs fail to be long-term maintained/expanded in vitro. We identified the anti-apoptotic protein CFLAR is down-regulated in those affected NPCs and ectopic expression of CFLAR rescues NPC defects induced by STAMBP-deficiency. Our study not only provides novel insight into the mechanism of neural defects in STAMBP mutant patients, it also indicates that the death receptor mediated apoptosis is an obstacle for long-term maintenance/expansion of NPCs in vitro thus counteracting this cell death pathway could be beneficial to the generation of NPCs in vitro.

3.
Reprod Sci ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977640

RESUMO

Management of cardiovascular disease in pregnancy is important, yet the association between cardiovascular health and infertility is rarely reported. In this study, we aimed to explore the association between Life's Essential 8 (LE8), a novel cardiovascular health (CVH) measure, and infertility, and to investigate potential mediating mechanisms. This study investigated cross-sectional data from the 2013-2018 National Health and Nutrition Examination Survey. LE8 score (ranging from 0 to 100) was calculated as the unweighted average of eight CVH metrics. The association between LE8 and infertility was explored through weighted multiple logistic regression. Restricted cubic splines were used to explore nonlinear correlation. In addition, mediation analysis was conducted to investigate the role of oxidative stress and inflammatory markers systematically. After strict exclusion criteria, 1703 American women aged 18-45 years were included. After full adjustment, the LE8 score showed a negative correlation with infertility [per 1 SD increase, OR = 0.675, 95% CI: 0.553-0.824], with a linear dose-response relationship (non-linear P = 0.122). Similar linear negative correlations were found between health factor scores and infertility, with higher body mass index and glucose scores having a significantly lower risk of infertility. Stratified analyses showed a stronger inversed relationship between LE8 and infertility in younger populations. Moreover, mediation analysis revealed that uric acid concentration and lymphocyte count mediated the effect of LE8 on infertility (P < 0.05). LE8 and its subscale scores were linearly and negatively associated with infertility, which may be mediated in part through uric acid and lymphocyte count. Focusing on weight management and glycemic control can effectively reduce the risk of infertility.

4.
Chin J Integr Med ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910189

RESUMO

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS: Patients with a nadir CT value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.

5.
J Control Release ; 371: 324-337, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823584

RESUMO

There is an urgent clinical need to develop nerve-blocking agents capable of inducing long duration sensory block without muscle weakness or paralysis to treat post-operative and chronic pain conditions. Here, we report a galacturonic acid-capsaicin (GalA-CAP) prodrug as an effective nociceptive-selective axon blocking agent. Capsaicin selectively acts on nociceptive signaling without motor nerve blockade or disruption of proprioception and touch sensation, and the galacturonic acid moiety enhance prodrug permeability across the restrictive peripheral nerve barriers (PNBs) via carrier-mediated transport by the facilitative glucose transporters (GLUTs). In addition, following prodrug transport across PNBs, the inactive prodrug is converted to active capsaicin through linker hydrolysis, leading to sustained drug release. A single injection of GalA-CAP prodrug at the sciatic nerves of rats led to nociceptive-selective nerve blockade lasting for 234 ± 37 h, which is a sufficient duration to address the most intense period of postsurgical pain. Furthermore, the prodrug markedly mitigated capsaicin-associated side effects, leading to a notable decrease in systemic toxicity, benign local tissue reactions, and diminished burning and irritant effects.


Assuntos
Capsaicina , Bloqueio Nervoso , Pró-Fármacos , Ratos Sprague-Dawley , Nervo Isquiático , Pró-Fármacos/administração & dosagem , Animais , Capsaicina/administração & dosagem , Capsaicina/análogos & derivados , Masculino , Nervo Isquiático/efeitos dos fármacos , Bloqueio Nervoso/métodos , Ratos , Analgésicos/administração & dosagem , Analgésicos/farmacologia
6.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 988-999, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856406

RESUMO

We propose a model-driven projected algebraic reconstruction technique (PART)-network (PART-Net) that leverages the advantages of the traditional model-based method and the neural network to improve the imaging quality of diffuse fluorescence tomography. In this algorithm, nonnegative prior information is incorporated into the ART iteration process to better guide the optimization process, and thereby improve imaging quality. On this basis, PART in conjunction with a residual convolutional neural network is further proposed to obtain high-fidelity image reconstruction. The numerical simulation results demonstrate that the PART-Net algorithm effectively improves noise robustness and reconstruction accuracy by at least 1-2 times and exhibits superiority in spatial resolution and quantification, especially for a small-sized target (r=2m m), compared with the traditional ART algorithm. Furthermore, the phantom and in vivo experiments verify the effectiveness of the PART-Net, suggesting strong generalization capability and a great potential for practical applications.

7.
Zool Res ; 45(4): 821-830, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38894524

RESUMO

Magnetic sense, or termed magnetoreception, has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation. MagRs, highly conserved A-type iron-sulfur proteins, are widely distributed across all phyla and play essential roles in both magnetoreception and iron-sulfur cluster biogenesis. However, the evolutionary origins and functional diversification of MagRs from their prokaryotic ancestor remain unclear. In this study, MagR sequences from 131 species, ranging from bacteria to humans, were selected for analysis, with 23 representative sequences covering species from prokaryotes to Mollusca, Arthropoda, Osteichthyes, Reptilia, Aves, and mammals chosen for protein expression and purification. Biochemical studies revealed a gradual increase in total iron content in MagRs during evolution. Three types of MagRs were identified, each with distinct iron and/or iron-sulfur cluster binding capacity and protein stability, indicating continuous expansion of the functional roles of MagRs during speciation and evolution. This evolutionary biochemical study provides valuable insights into how evolution shapes the physical and chemical properties of biological molecules such as MagRs and how these properties influence the evolutionary trajectories of MagRs.


Assuntos
Proteínas Ferro-Enxofre , Animais , Proteínas Ferro-Enxofre/genética , Proteínas Ferro-Enxofre/metabolismo , Proteínas Ferro-Enxofre/química , Evolução Biológica , Evolução Molecular , Filogenia , Ferro/metabolismo
8.
Crit Rev Food Sci Nutr ; : 1-16, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795064

RESUMO

Macular carotenoids, which consist of lutein, zeaxanthin, and meso-zeaxanthin, are dietary antioxidants and macular pigments in the eyes, protecting the macula from light-induced oxidative stress. Lutein is also the main carotenoid in the infant brain and is involved in cognitive development. While a few articles reviewed the role of lutein in early health and development, the current review is the first that focuses on the outcomes of lutein supplementation, either provided to mothers or to infants. Additionally, lutein status and metabolism during pregnancy and lactation, factors that limit the potential application of lutein as a nutritional intervention, and solutions to overcome the limitation are also discussed. In brief, the lutein intake in pregnant and lactating women in the United States may not be optimal. Furthermore, preterm and formula-fed infants are known to have compromised lutein status compared to term and breast-fed infants, respectively. While lutein supplementation via both maternal and infant consumption improves lutein status in infants, the application of lutein as a nutritional intervention may be compromised by its low bioavailability. Various encapsulation techniques have been developed to enhance the delivery of lutein in adult animals or human but should be further evaluated in neonatal models.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38771684

RESUMO

Flexible robots (FRs) are generally designed to be lightweight to achieve rapid motion. However, accompanying vibrations and modeling errors influence tracking control, especially in situations involving reference signal loss. This article develops a two-time scale primal-dual inverse reinforcement learning (PD-IRL) framework for FRs to perform tracking tasks with incomplete reference signals. First, consider the admissible policy as a nonconvex input constraint to guarantee the stable operation of the equipment. Then, FRs imitate the demonstration behaviors of an expert, including both rigid and flexible motions, to achieve a balance in tracking speed and vibration suppression. During the imitation process, nonconvex optimization problems of FRs are transformed into corresponding dual problems to obtain the global optimal policy. Moreover, employing multiple linearly independent paths to explore the state space simultaneously can improve convergence speed. Convergence and stability are studied rigorously. Finally, simulations and comparisons show the effectiveness and superiority of the proposed method.

10.
Synth Syst Biotechnol ; 9(3): 522-530, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38645975

RESUMO

The morphology is the consequence of evolution and adaptation. Escherichia coli is rod-shaped bacillus with regular dimension of about 1.5 µm long and 0.5 µm wide. Many shape-related genes have been identified and used in morphology engineering of this bacteria. However, little is known about if specific metabolism and metal irons could modulate bacteria morphology. Here in this study, we discovered filamentous shape change of E. coli cells overexpressing pigeon MagR, a putative magnetoreceptor and extremely conserved iron-sulfur protein. Comparative transcriptomic analysis strongly suggested that the iron metabolism change and iron accumulation due to the overproduction of MagR was the key to the morphological change. This model was further validated, and filamentous morphological change was also achieved by supplement E. coli cells with iron in culture medium or by increase the iron uptake genes such as entB and fepA. Our study extended our understanding of morphology regulation of bacteria, and may also serves as a prototype of morphology engineering by modulating the iron metabolism.

11.
Biomed Opt Express ; 15(4): 2078-2093, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38633070

RESUMO

To alleviate the ill-posedness of diffuse fluorescence tomography (DFT) reconstruction and improve imaging quality and speed, a model-derived deep-learning method is proposed by combining extended Kalman filtering (EKF) with a long short term memory (LSTM) neural network, where the iterative process parameters acquired by implementing semi-iteration EKF (SEKF) served as inputs to the LSTM neural network correction model for predicting the optimal fluorescence distributions. To verify the effectiveness of the SEKF-LSTM algorithm, a series of numerical simulations, phantom and in vivo experiments are conducted, and the experimental results are quantitatively evaluated and compared with the traditional EKF algorithm. The simulation experimental results show that the proposed new algorithm can effectively improve the reconstructed image quality and reconstruction speed. Importantly, the LSTM correction model trained by the simulation data also obtains satisfactory results in the experimental data, suggesting that the SEKF-LSTM algorithm possesses strong generalization ability and great potential for practical applications.

12.
Zool Res ; 45(3): 468-477, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38583938

RESUMO

Iron-sulfur clusters are essential cofactors for proteins involved in various biological processes, such as electron transport, biosynthetic reactions, DNA repair, and gene expression regulation. Iron-sulfur cluster assembly protein IscA1 (or MagR) is found within the mitochondria of most eukaryotes. Magnetoreceptor (MagR) is a highly conserved A-type iron and iron-sulfur cluster-binding protein, characterized by two distinct types of iron-sulfur clusters, [2Fe-2S] and [3Fe-4S], each conferring unique magnetic properties. MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome (Cry) and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation. Although the N-terminal sequences of MagR vary among species, their specific function remains unknown. In the present study, we found that the N-terminal sequences of pigeon MagR, previously thought to serve as a mitochondrial targeting signal (MTS), were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound. Moreover, the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex. Thus, the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting. These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.


Assuntos
Proteínas Ferro-Enxofre , Animais , Proteínas Ferro-Enxofre/genética , Proteínas Ferro-Enxofre/química , Proteínas Ferro-Enxofre/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Ferro/metabolismo , Enxofre/metabolismo
13.
Stem Cell Res ; 77: 103420, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643711

RESUMO

PPM1A is a member of the serine/threonine protein phosphatase family. It can bind to a variety of proteins to dephosphorylate them, and extensively regulates many life activities such as cell growth, cell stress, immune response, and tumor formation. Here we constructed a human induced pluripotent stem cell (hiPSC) line with knockout of PPM1A using CRISPR/Cas9-mediated gene targeting. This cell line exhibits normal karyotype, pluripotency, and trilineage differentiation potential, which could provide a useful cellular resource for exploring the mechanism of PPM1A in regulating downstream signaling pathways and explore the application of PPM1A in anti-tumor and anti-infection.


Assuntos
Sistemas CRISPR-Cas , Células-Tronco Pluripotentes Induzidas , Proteína Fosfatase 2C , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Proteína Fosfatase 2C/metabolismo , Proteína Fosfatase 2C/genética , Diferenciação Celular , Linhagem Celular
14.
Int J Surg ; 110(6): 3580-3590, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626431

RESUMO

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×10 3  U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group ( n =179 patients) and the normalization group ( n =73 patients) had better OS and RFS than the non-normalization group ( n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P <0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.


Assuntos
Bilirrubina , Antígeno CA-19-9 , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Estudos Retrospectivos , Bilirrubina/sangue , Feminino , Masculino , Antígeno CA-19-9/sangue , Pessoa de Meia-Idade , Idoso , Prognóstico , Adulto
15.
Chemosphere ; 355: 141825, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552802

RESUMO

BACKGROUND: Most research exploring the correlation between volatile organic compounds (VOCs) and hematological parameters have focused on single VOCs. Our study aimed to explore the single and combined effects of VOCs on hematological parameters through three statistical models. METHODS: Data from 4 cycles of the National Health and Nutrition Examination Survey (NHANES) were used in this study. The correlations between single exposure to 16 VOCs and hematological parameters in the general population were assessed by weighted multiple linear regression. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were used to explore the relationship between the combined important VOCs selected by the least absolute shrinkage and selection operator (LASSO) and hematological parameters, as well as the effects of smoking status on them. RESULTS: A total of 4089 adults were included in the study. We found that a variety of VOCs were significantly associated with hematological parameters. Among them, N-acetyl-S-(benzyl)-l-cysteine (BMA) was significantly negatively correlated with white blood cell (WBC), red blood cell (RBC), lymphocyte, and neutrophil counts. N-acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine (HPMMA) was significantly positively correlated with WBC, monocyte, lymphocyte, and neutrophil counts. In the WQS analysis, the WQS index of the VOCs mixtures was positively correlated with WBC (ß: 0.031; P < 0.001), monocyte (0.023; P = 0.021), and neutrophil (0.040; P = 0.001) counts, while negatively associated with RBC (-0.013; P < 0.001) counts. The BKMR model revealed that combined exposure to VOCs levels ≥70th percentile was significantly associated with lower RBC counts, and BMA was identified as the dominant contributor. Smoking significantly influenced the relationship between VOCs and hematological parameters. CONCLUSIONS: Our study indicated the effects of single and overall VOCs exposure on hematological parameters and suggested the hematotoxicity as well as pro-inflammatory effects of VOCs, which had strong public health implications for reducing the potential health hazards of VOCs exposure to the hematologic system.


Assuntos
Exposição Ambiental , Compostos Orgânicos Voláteis , Adulto , Humanos , Exposição Ambiental/análise , Inquéritos Nutricionais , Compostos Orgânicos Voláteis/toxicidade , Fumar , Teorema de Bayes , Cisteína
16.
Biomaterials ; 306: 122498, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38310828

RESUMO

Magnetic hyperthermia therapy (MHT) has garnered immense interest due to its exceptional spatiotemporal specificity, minimal invasiveness and remarkable tissue penetration depth. Nevertheless, the limited magnetothermal heating capability and the potential toxicity of metal ions in magnetic materials based on metallic elements significantly impede the advancement of MHT. Herein, we introduce the concept of nonmetallic materials, with graphite (Gra) as a proof of concept, as a highly efficient and biocompatible option for MHT of tumors in vivo for the first time. The Gra exhibits outstanding magnetothermal heating efficacy owing to the robust eddy thermal effect driven by its excellent electrical conductivity. Furthermore, being composed of carbon, Gra offers superior biocompatibility as carbon is an essential element for all living organisms. Additionally, the Gra boasts customizable shapes and sizes, low cost, and large-scale production capability, facilitating reproducible and straightforward manufacturing of various Gra implants. In a mouse tumor model, Gra-based MHT successfully eliminates the tumors at an extremely low magnetic field intensity, which is less than one-third of the established biosafety threshold. This study paves the way for the development of high-performance magnetocaloric materials by utilizing nonmetallic materials in place of metallic ones burdened with inherent limitations.


Assuntos
Grafite , Hipertermia Induzida , Neoplasias , Animais , Camundongos , Neoplasias/terapia , Campos Magnéticos
17.
J Biophotonics ; 17(5): e202300493, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38329194

RESUMO

IR780 iodide is a commercially available targeted near-infrared contrast agent for in vivo imaging and cancer photodynamic or photothermal therapy, whereas the accumulation, dynamics, and retention of IR780 in biological tissue, especially in tumor is still under-explored. Diffuse fluorescence tomography (DFT) can be used for localization and quantification of the three-dimensional distribution of NIR fluorophores. Herein, a homemade DFT imaging system combined with tumor-targeted IR780 was utilized for cancer imaging and pharmacokinetic evaluation. The aim of this study is to comprehensively assess the biochemical and pharmacokinetic characteristics of IR780 with the aid of DFT imaging. The optimal IR780 concentration (20 µg/mL) was achieved first. Subsequently, the good biocompatibility and cellar uptake of IR780 was demonstrated through the mouse acute toxic test and cell assay. In vivo, DFT imaging effectively identified various subcutaneous tumors and revealed the long-term retention of IR780 in tumors and rapid metabolism in the liver. Ex vivo imaging indicated IR780 was mainly concentrated in tumor and lung with significantly different from the distribution in other organs. DFT imaging allowed sensitive tumor detection and pharmacokinetic rates analysis. Simultaneously, the kinetics of IR780 in tumors and liver provided more valuable information for application and development of IR780.


Assuntos
Indóis , Animais , Camundongos , Linhagem Celular Tumoral , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Tomografia , Distribuição Tecidual , Imagem Óptica , Tomografia Óptica/métodos
18.
Nucleic Acids Res ; 52(9): 4935-4949, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38421638

RESUMO

TGF-ß signaling family plays an essential role to regulate fate decisions in pluripotency and lineage specification. How the action of TGF-ß family signaling is intrinsically executed remains not fully elucidated. Here, we show that HBO1, a MYST histone acetyltransferase (HAT) is an essential cell intrinsic determinant for TGF-ß signaling in human embryonic stem cells (hESCs). HBO1-/- hESCs fail to response to TGF-ß signaling to maintain pluripotency and spontaneously differentiate into neuroectoderm. Moreover, HBO1 deficient hESCs show complete defect in mesendoderm specification in BMP4-triggered gastruloids or teratomas. Molecularly, HBO1 interacts with SMAD4 and co-binds the open chromatin labeled by H3K14ac and H3K4me3 in undifferentiated hESCs. Upon differentiation, HBO1/SMAD4 co-bind and maintain the mesoderm genes in BMP4-triggered mesoderm cells while lose chromatin occupancy in neural cells induced by dual-SMAD inhibition. Our data reveal an essential role of HBO1, a chromatin factor to determine the action of SMAD in both human pluripotency and mesendoderm specification.


Assuntos
Diferenciação Celular , Histona Acetiltransferases , Mesoderma , Transdução de Sinais , Proteína Smad4 , Humanos , Proteína Morfogenética Óssea 4/metabolismo , Proteína Morfogenética Óssea 4/genética , Linhagem Celular , Cromatina/metabolismo , Endoderma/citologia , Endoderma/metabolismo , Histona Acetiltransferases/metabolismo , Histona Acetiltransferases/genética , Histonas/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Mesoderma/metabolismo , Mesoderma/citologia , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , Proteína Smad4/metabolismo , Proteína Smad4/genética , Fator de Crescimento Transformador beta/metabolismo
19.
J Virol ; 98(3): e0146923, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38345385

RESUMO

Grass carp reovirus (GCRV), particularly the highly prevalent type II GCRV (GCRV-II), causes huge losses in the aquaculture industry. However, little is known about the mechanisms by which GCRV-II invades grass carp and further disseminates among tissues. In the present study, monocytes/macrophages (Mo/Mφs) were isolated from the peripheral blood of grass carp and infected with GCRV-II. The results of indirect immunofluorescent microscopy, transmission electron microscopy, real-time quantitative RT-PCR (qRT-PCR), western blot (WB), and flow cytometry analysis collectively demonstrated that GCRV-II invaded Mo/Mφs and replicated in them. Additionally, we observed that GCRV-II induced different types (M1 and M2) of polarization of Mo/Mφs in multiple tissues, especially in the brain, head kidney, and intestine. To assess the impact of different types of polarization on GCRV-II replication, we recombinantly expressed and purified the intact cytokines CiIFN-γ2, CiIL-4/13A, and CiIL-4/13B and successfully induced M1 and M2 type polarization of macrophages using these cytokines through in vitro experiments. qRT-PCR, WB, and flow cytometry analyses showed that M2 macrophages had higher susceptibility to GCRV-II infection than other types of Mo/Mφs. In addition, we found GCRV-II induced apoptosis of Mo/Mφs to facilitate virus replication and dissemination and also detected the presence of GCRV-II virus in plasma. Collectively, our findings indicated that GCRV-II could invade immune cells Mo/Mφs and induce apoptosis and polarization of Mo/Mφs for efficient infection and dissemination, emphasizing the crucial role of Mo/Mφs as a vector for GCRV-II infection.IMPORTANCEType II grass carp reovirus (GCRV) is a prevalent viral strain and causes huge losses in aquaculture. However, the related dissemination pathway and mechanism remain largely unclear. Here, our study focused on phagocytic immune cells, monocytes/macrophages (Mo/Mφs) in blood and tissues, and explored whether GCRV-II can invade Mo/Mφs and replicate and disseminate via Mo/Mφs with their differentiated type M1 and M2 macrophages. Our findings demonstrated that GCRV-II infected Mo/Mφs and replicated in them. Furthermore, GCRV-II infection induces an increased number of M1 and M2 macrophages in grass carp tissues and a higher viral load in M2 macrophages. Furthermore, GCRV-II induced Mo/Mφs apoptosis to release viruses, eventually infecting more cells. Our study identified Mo/Mφs as crucial components in the pathway of GCRV-II dissemination and provides a solid foundation for the development of treatment strategies for GCRV-II infection.


Assuntos
Carpas , Doenças dos Peixes , Orthoreovirus , Infecções por Reoviridae , Animais , Apoptose , Citocinas , Doenças dos Peixes/metabolismo , Doenças dos Peixes/patologia , Doenças dos Peixes/virologia , Macrófagos/metabolismo , Macrófagos/patologia , Macrófagos/virologia , Monócitos/metabolismo , Infecções por Reoviridae/metabolismo , Infecções por Reoviridae/patologia , Infecções por Reoviridae/veterinária , Replicação Viral
20.
Foods ; 13(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38397583

RESUMO

The North China type cucumber, characterized by its dense spines and top flowers, is susceptible to damage during the grading process, affecting its market value. Moreover, traditional manual grading methods are time-consuming and labor-intensive. To address these issues, this paper proposes a cucumber quality grader based on machine vision and deep learning. In the electromechanical aspect, a novel fixed tray type grading mechanism is designed to prevent damage to the vulnerable North China type cucumbers during the grading process. In the vision grading algorithm, a new convolutional neural network is introduced named MassNet, capable of predicting cucumber mass using only a top-view image. After obtaining the cucumber mass prediction, mass grading is achieved. Experimental validation includes assessing the electromechanical performance of the grader, comparing MassNet with different models in predicting cucumber mass, and evaluating the online grading performance of the integrated algorithm. Experimental results indicate that the designed cucumber quality grader achieves a maximum capacity of 2.3 t/hr. In comparison with AlexNet, MobileNet, and ResNet, MassNet demonstrates superior cucumber mass prediction, with a MAPE of 3.9% and RMSE of 6.7 g. In online mass grading experiments, the grading efficiency of the cucumber quality grader reaches 93%.

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