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1.
Aging (Albany NY) ; 162024 May 28.
Article in English | MEDLINE | ID: mdl-38809507

ABSTRACT

Intracerebral hemorrhage (ICH) can induce intensive oxidative stress, neuroinflammation, and brain cell apoptosis. However, conventional methods for ICH treatment have many disadvantages. There is an urgent need for alternative, effective therapies with minimal side effects. Pharmacodynamics experiment, molecular docking, network pharmacology, and metabolomics were adopted to investigate the treatment and its mechanism of Jingfang Granules (JFG) in ICH. In this study, we investigated the therapeutic effects of JFG on ICH using behavioral, brain water content and Magnetic resonance imaging experiments. However, the key active component and targets of JFG remain unknown. Here we verified that JFG was beneficial to improve brain injury after ICH. A network pharmacology analysis revealed that the anti-inflammatory effect of JFG is predominantly mediated by its activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway through Luteolin, (+)-Anomalin and Phaseol and their targeting of AKT1, tumor necrosis factorα (TNF-α), and interleukin-1ß (IL-1ß). Molecular docking analyses revealed an average affinity of -8.633 kcal/mol, indicating a binding strength of less than -5 kcal/mol. Metabolomic analysis showed that JFG exerted its therapeutic effect on ICH by regulating metabolic pathways, such as the metabolism of taurine and hypotaurine, biosynthesis of valine, leucine, and isoleucine. In conclusion, we demonstrated that JFG attenuated neuroinflammation and BBB injury subsequent to ICH by activating the PI3K/Akt signaling pathway.

2.
Anal Bioanal Chem ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691170

ABSTRACT

The utilization of supramolecular deep eutectic solvent eddy-assisted liquid-liquid microextraction utilizing 2-hydroxypropyl ß-cyclodextrin (SUPRADES) has been identified as a successful method for pre-enriching Cu, Zn, and Mn in vegetable oil samples. Determination of each element was conducted by inductively coupled plasma optical emission spectrometry (ICP-OES) after digestion of metal-enriched phases. Various parameters were examined, including the composition of SUPRADES species [2HP-ß-CD: DL-lactic acid], a cyclodextrin mass ratio of 20 wt%, a water bath temperature of 75 °C, an extractor volume of 800 µL, a dispersant volume of 50 µL, and an eddy current time of 5 min. Optimal conditions resulted in extraction rates of 99.6% for Cu, 105.2% for Zn, and 101.5% for Mn. The method exhibits a broad linear range spanning from 10 to 20,000 µg L-1, with determination coefficients exceeding 0.99 for all analytes. Enrichment coefficients of 24, 21, and 35 were observed. Limits of detection ranged from 0.89 to 1.30 µg L-1, while limits of quantification ranged from 3.23 to 4.29 µg L-1. The unique structural characteristics of the method enable the successful determination of trace elements in a variety of edible vegetable oils.

3.
Minerva Urol Nephrol ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38757773

ABSTRACT

BACKGROUND: A three-dimensional (3D) reconstruction of the kidney, parapelvic cyst and the collecting system was conducted using the 3D Slicer software. The reconstructed image was used to form a virtual endoscope to assist flexible ureteroscopic incision and drainage was performed with a holmium laser for treating parapelvic cysts. The effectiveness of this assistive technique was assessed. METHODS: This was a retrospective cohort study. The clinical information of 59 patients undergoing flexible ureteroscopic incision and drainage for parapelvic cysts in two medical centers was collected. 3D Slicer software reconstruction and virtual endoscopic imaging were performed for 28 cases. Before the operation, the best point for incision on the collecting system's mucosa was assessed by virtual endoscope imaging. Propensity score matching was adopted for the reconstructive and non-reconstructive groups. RESULTS: After matching, the reconstructive group and non-reconstructive group both had 21 cases each. The operation time in the reconstructive and non-reconstructive groups was 38.81±5.01 and 51.00±18 minutes, respectively. Statistically significant differences existed between the two groups (t=7.024, P<0.001). No statistical significance was found in postoperative fever, immediate postoperative C reactive protein (CRP), length of postoperative hospital stay and cyst diameter three months after the operation. CONCLUSIONS: The operator was provided with a more direct and real vision when 3D Slicer software reconstruction was adopted via virtual endoscopic imaging to assist flexible ureteroscopic parapelvic cyst incision. This helped reduce the operation time. Further follow-ups and observations are required to assess the long-term efficacy of flexible ureteroscopic parapelvic cyst incision.

4.
ACS Appl Mater Interfaces ; 16(19): 25246-25255, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38696547

ABSTRACT

Ion transportation via the mixed mechanisms of hydrogels underpins ultrafast biological signal transmission in nature, and its application to the rapid and sensitive sensing detection of human specific ions is of great interest for the field of medical science. However, current research efforts are still unable to achieve transmission results that are comparable to those of bioelectric signals. Herein, 3D interconnected nanochannels based on poly(pyrrole-co-dopamine)/poly(vinyl alcohol) (P(Py-co-DA)/PVA) supernetwork conductive hydrogels are designed and fabricated as stimuli-responsive structures for K+ ions. Distinct from conventional configurations, which exhibit rapid electron transfer and permeability to biosubstrates, interconnected nanofluidic nanochannels collaborated with the P(Py-co-DA) conductive polymer in the supernetwork conductive hydrogel significantly improve conductivity (88.3 mS/cm), ion transport time (0.1 s), and ion sensitivity (74.6 mV/dec). The faster ion response time is attributed to the synergism of excellent conductivity originating from the P(Py-co-DA) polymer and the electronic effect in the interconnected nanofluidic channels. Furthermore, the supernetwork conductive hydrogel demonstrates K+ ion selectivity relative to other cations in biofluids such as Na+, Mg2+, and Ca2+. The DFT calculation indicates that the small solvation energy and low chemical transfer resistance are the main reasons for the excellent K+ ion selectivity. Finite element analysis (FEA) simulations further support these experimental results. Consequently, the P(Py-co-DA)/PVA supernetwork conductive hydrogels enriched with the 3D interconnected nanofluidic channels developed in this work possess excellent sensing of K+ ions. This strategy provides great insight into efficient ion sensing in traditional biomedical sensing that has not been explored by previous researchers.

5.
Int J Mol Sci ; 25(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38732032

ABSTRACT

Fruit shape is an important external feature when consumers choose their preferred fruit varieties. Studying persimmon (Diospyros kaki Thunb.) fruit shape is beneficial to increasing its commodity value. However, research on persimmon fruit shape is still in the initial stage. In this study, the mechanism of fruit shape formation was studied by cytological observations, phytohormone assays, and transcriptome analysis using the long fruit and flat fruit produced by 'Yaoxianwuhua' hermaphroditic flowers. The results showed that stage 2-3 (June 11-June 25) was the critical period for persimmon fruit shape formation. Persimmon fruit shape is determined by cell number in the transverse direction and cell length in the longitudinal direction. High IAA, GA4, ZT, and BR levels may promote long fruit formation by promoting cell elongation in the longitudinal direction, and high GA3 and ABA levels may be more conducive to flat fruit formation by increasing the cell number in the transverse direction and inhibiting cell elongation in the longitudinal direction, respectively. Thirty-two DEGs related to phytohormone biosynthesis and signaling pathways and nine DEGs related to cell division and cell expansion may be involved in the persimmon fruit shape formation process. These results provide valuable information for regulatory mechanism research on persimmon fruit formation.


Subject(s)
Diospyros , Fruit , Gene Expression Profiling , Gene Expression Regulation, Plant , Plant Growth Regulators , Diospyros/genetics , Diospyros/metabolism , Diospyros/growth & development , Fruit/genetics , Fruit/metabolism , Fruit/growth & development , Plant Growth Regulators/metabolism , Gene Expression Profiling/methods , Transcriptome , Plant Proteins/metabolism , Plant Proteins/genetics , Flowers/genetics , Flowers/metabolism , Flowers/growth & development
6.
Sensors (Basel) ; 24(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38732933

ABSTRACT

This paper investigates a method for precise mapping of human arm movements using sEMG signals. A multi-channel approach captures the sEMG signals, which, combined with the accurately calculated joint angles from an Inertial Measurement Unit, allows for action recognition and mapping through deep learning algorithms. Firstly, signal acquisition and processing were carried out, which involved acquiring data from various movements (hand gestures, single-degree-of-freedom joint movements, and continuous joint actions) and sensor placement. Then, interference signals were filtered out through filters, and the signals were preprocessed using normalization and moving averages to obtain sEMG signals with obvious features. Additionally, this paper constructs a hybrid network model, combining Convolutional Neural Networks and Artificial Neural Networks, and employs a multi-feature fusion algorithm to enhance the accuracy of gesture recognition. Furthermore, a nonlinear fitting between sEMG signals and joint angles was established based on a backpropagation neural network, incorporating momentum term and adaptive learning rate adjustments. Finally, based on the gesture recognition and joint angle prediction model, prosthetic arm control experiments were conducted, achieving highly accurate arm movement prediction and execution. This paper not only validates the potential application of sEMG signals in the precise control of robotic arms but also lays a solid foundation for the development of more intuitive and responsive prostheses and assistive devices.


Subject(s)
Algorithms , Arm , Electromyography , Movement , Neural Networks, Computer , Signal Processing, Computer-Assisted , Humans , Electromyography/methods , Arm/physiology , Movement/physiology , Gestures , Male , Adult
7.
Inorg Chem ; 63(20): 9288-9296, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38724469

ABSTRACT

A novel 3D europium-based cationic framework (Eu-CMOF) has been constructed solvothermally by employing a viologen derivative as an organic functional building unit. Notably, Eu-CMOF demonstrates its capability as a proficient aqueous-phase ion-exchange host, facilitating the remarkable rapid chromatographic column separation of new coccine and malachite green (NC3-/MG+), as well as new coccine and methylene blue (NC3-/MLB+), in mere 2 to 4 min. Adsorption thermodynamics and kinetics of anionic dyes demonstrate that Eu-CMOF exhibits a higher adsorption capacity for NC3-, as evaluated by the Langmuir model, reaching a value of 173 mg·g-1. The pseudo-second-order rate constant is determined to be 3.84 × 10-3 mg-1·g·min-1. Additionally, Eu-CMOF displays reversible photochromic and amine- and ammonia-induced vapochromic behaviors. Further mechanistic studies reveal that these chromic behaviors are primarily attributed to the generation of free viologen radical stimulated by Xe-light or electron-rich amine/ammonia. This research contributes to the development of advanced materials with applications in rapid chromatographic separation and stimuli-responsive chromic properties, showcasing the potential of Eu-CMOF as a versatile platform for practical applications.

8.
Neurooncol Adv ; 6(1): vdae036, 2024.
Article in English | MEDLINE | ID: mdl-38721358

ABSTRACT

Background: Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in multiple countries, including the USA (≥ 2 years). Until recently, individuals had to take selumetinib twice daily (BID) in a fasted state. This study evaluated the effect of a low-fat meal on selumetinib PK parameters and gastrointestinal (GI) tolerability in adolescent participants with NF1-PN. Methods: Eligible participants aged ≥ 12 to < 18 years took 25 mg/m2 selumetinib BID with a low-fat meal (T1) for 28 days, followed by a 7-day washout, and then administration in a fasted state (T2) for another 28 days. Primary objectives were to evaluate the effect of a low-fat meal on AUC0-12,ss and GI tolerability after multiple selumetinib doses in T1 versus T2. Key secondary objectives were additional PK parameters and adverse events (AEs). Results: At primary data cut-off, all 24 participants completed T1, and 23 participants completed T2. There were no significant differences in AUC0-12,ss between T1 and T2. In T1 and T2, 29.2% and 33.3% participants, respectively, reported ≥ 1 GI AE. No GI AEs Grade ≥ 3, or serious AEs, or GI AEs resulting in treatment interruptions, discontinuation, or dose reductions were reported in T1 and T2. Conclusions: Dosing selumetinib with a low-fat meal had no clinically relevant impact on selumetinib AUC0-12,ss nor GI tolerability in adolescents with NF1-PN. Trial registration ClinicalTrialsgov ID: NCT05101148.

9.
BMC Cancer ; 24(1): 480, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627684

ABSTRACT

BACKGROUND: The treatment of hepatocellular carcinoma (HCC) patients exhibiting high-risk characteristics (Vp4, and/or bile duct invasion, and/or tumor occupancy ≥ 50%) lacks standardized approaches and yields unfavorable results. This study endeavors to evaluate the safety, efficacy, and prognostic impacts of employing hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1 (PD-1) in the treatment of high-risk HCC patients. METHODS: In this retrospective analysis, HCC patients with high-risk features were treated with either lenvatinib combined with PD-1 (LEN-PD1) or a combination of HAIC, lenvatinib, and PD-1 (HAIC-LEN-PD1). The study assessed the antitumor efficacy by calculating overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. RESULTS: Between June 2019 and September 2022, a total of 61 patients were included in the LEN-PD1 group, while 103 patients were enrolled in the HAIC-LEN-PD1 group. The OS was 9.8 months in the LEN-PD1 group, whereas the HAIC-LEN-PD1 group exhibited a significantly longer median OS of 19.3 months (HR = 0.43, p < 0.001). Furthermore, PFS was notably extended in the HAIC-LEN-PD1 group compared to the LEN-PD1 group (9.6 months vs. 4.9 months, HR = 0.48, p < 0.001). Patients in the HAIC-LEN-PD1 group had a higher ORR and DCR according to the modified RECIST (76.7% vs. 23.0%, p < 0.001; 92.2% vs. 72.1%, p = 0.001). HAIC-LEN-HAIC group led to more adverse events than LEN-PD1 group, most of which were tolerable and controllable. CONCLUSION: Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Phenylurea Compounds , Quinolines , Humans , Carcinoma, Hepatocellular/drug therapy , Programmed Cell Death 1 Receptor , Retrospective Studies , Liver Neoplasms/drug therapy
10.
Pathology ; 56(4): 516-527, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38570266

ABSTRACT

Matrix Gla protein (MGP) and trichorhinophalangeal syndrome type 1 (TRPS1) have recently emerged as novel breast-specific immunohistochemical (IHC) markers, particularly for triple-negative breast cancer (TNBC) and metaplastic carcinoma. The present study aimed to validate and compare the expression of MGP, TRPS1 and GATA binding protein 3 (GATA3) in metastatic breast carcinoma (MBC), invasive breast carcinoma (IBC) with special features, including special types of invasive breast carcinoma (IBC-STs) and invasive breast carcinoma of no special type with unique features, and mammary and non-mammary salivary gland-type tumours (SGTs). Among all enrolled cases, MGP, TRPS1 and GATA3 had comparable high positivity for ER/PR-positive (p=0.148) and HER2-positive (p=0.310) breast carcinoma (BC), while GATA3 positivity was significantly lower in TNBC (p<0.001). Similarly, the positive rates of MGP and TRPS1 in MBCs (99.4%), were higher than in GATA3 (90.9%, p<0.001). Among the IBC-STs, 98.4% of invasive lobular carcinomas (ILCs) were positive for all three markers. Among neuroendocrine tumours (NTs), all cases were positive for TRPS1 and GATA3, while MGP positivity was relatively low (81.8%, p=0.313). In the neuroendocrine carcinoma (NC) subgroup, all cases were positive for GATA3 and MGP, while one case was negative for TRPS1. All carcinomas with apocrine differentiation (APOs) were positive for GATA3 and MGP, while only 60% of the cases demonstrated moderate staining for TRPS1. Among mammary SGTs, MGP demonstrated the highest positivity (100%), followed by TRPS1 (96.0%) and GATA3 (72.0%). Positive staining for these markers was also frequently observed in non-mammary SGTs. Our findings further validate the high sensitivity of MGP and TRPS1 in MBCs, IBC-STs, and breast SGTs. However, none of these markers are capable of distinguishing between mammary and non-mammary SGTs.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Calcium-Binding Proteins , DNA-Binding Proteins , Extracellular Matrix Proteins , GATA3 Transcription Factor , Matrix Gla Protein , Repressor Proteins , Salivary Gland Neoplasms , Transcription Factors , Humans , GATA3 Transcription Factor/metabolism , GATA3 Transcription Factor/analysis , Female , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Breast Neoplasms/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Repressor Proteins/metabolism , Middle Aged , Transcription Factors/metabolism , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/analysis , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/diagnosis , Salivary Gland Neoplasms/metabolism , Adult , Extracellular Matrix Proteins/metabolism , Aged , DNA-Binding Proteins/metabolism , Immunohistochemistry , Sensitivity and Specificity , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/metabolism , Aged, 80 and over
11.
Cancer Lett ; 590: 216868, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38593920

ABSTRACT

While previous studies have indicated the involvement of Isthmin 1 (ISM1), a secreted protein, in cancer development, the precise mechanisms have remained elusive. In this study, we unveiled that ISM1 is significantly overexpressed in both the blood and tissue samples of colorectal cancer (CRC) patients, correlating with their poor prognosis. Functional experiments demonstrated that enforced ISM1 expression significantly enhances CRC proliferation, migration, invasion and tumor growth. Notably, our investigation reveals an interaction of ISM1 with epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase (RTK) family of CRC cells. The binding of ISM1 triggered EGFR activation and initiate downstream signaling pathways. Meanwhile, intracellular ISM1 interacted with Y-box binding protein 1 (YBX1), enhancing its transcriptional regulation on EGFR. Furthermore, our research uncovered the regulation of ISM1 expression by the hypoxia-inducible transcription factor HIF-1α in CRC cells. Mechanistically, we identified HIF-1α as a direct regulator of ISM1, binding to a hypoxia response element on its promoter. This novel mechanism illuminated potential therapeutic targets, offering insights into restraining HIF-1α/ISM1/EGFR-driven CRC progression and metastasis.


Subject(s)
Cell Proliferation , Colorectal Neoplasms , Disease Progression , ErbB Receptors , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit , Y-Box-Binding Protein 1 , Humans , ErbB Receptors/metabolism , ErbB Receptors/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Y-Box-Binding Protein 1/metabolism , Y-Box-Binding Protein 1/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Animals , Cell Movement , Cell Line, Tumor , Mice , Male , Signal Transduction , Female , Mice, Nude , HCT116 Cells , Prognosis
12.
Vaccines (Basel) ; 12(4)2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38675730

ABSTRACT

Nanoparticles (NPs) have been widely utilized in vaccine design. Although numerous NPs have been explored, NPs with adjuvant effects on their own have rarely been reported. We produce a promising self-assembled NP by integrating the pentameric Escherichia coli heat-labile enterotoxin B subunit (LTB) (studied as a vaccine adjuvant) with a trimer-forming peptide. This fusion protein can self-assemble into the NP during expression, and polysaccharide antigens (OPS) are then loaded in vivo using glycosylation. We initially produced two Salmonella paratyphi A conjugate nanovaccines using two LTB subfamilies (LTIB and LTIIbB). After confirming their biosafety in mice, the data showed that both nanovaccines (NP(LTIB)-OPSSPA and NP(LTIIbB)-OPSSPA) elicited strong polysaccharide-specific antibody responses, and NP(LTIB)-OPS resulted in better protection. Furthermore, polysaccharides derived from Shigella or Klebsiella pneumoniae were loaded onto NP(LTIB) and NP(LTIIbB). The animal experimental results indicated that LTIB, as a pentamer module, exhibited excellent protection against lethal infections. This effect was also consistent with that of the reported cholera toxin B subunit (CTB) modular NP in all three models. For the first time, we prepared a novel promising self-assembled NP based on LTIB. In summary, these results indicated that the LTB-based nanocarriers have the potential for broad applications, further expanding the library of self-assembled nanocarriers.

13.
Nanomaterials (Basel) ; 14(8)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38668222

ABSTRACT

Nanoparticles (NPs) have been surfacing as a pivotal platform for vaccine development. In our previous work, we developed a cholera toxin B subunit (CTB)-based self-assembled nanoparticle (CNP) and produced highly promising bioconjugate nanovaccines by loading bacterial polysaccharide (OPS) in vivo. In particular, the Klebsiella pneumoniae O2 serotype vaccine showcased a potent immune response and protection against infection. However, extremely low yields limited its further application. In this study, we prepared an efficient Klebsiella pneumoniae bioconjugate nanovaccine in Escherichia coli with a very high yield. By modifying the 33rd glycine (G) in the CNP to aspartate (D), we were able to observe a dramatically increased expression of glycoprotein. Subsequently, through a series of mutations, we determined that G33D was essential to increasing production. In addition, this increase only occurred in engineered E. coli but not in the natural host K. pneumoniae strain 355 (Kp355) expressing OPSKpO2. Next, T-cell epitopes were fused at the end of the CNP(G33D), and animal experiments showed that fusion of the M51 peptide induced high antibody titers, consistent with the levels of the original nanovaccine, CNP-OPSKpO2. Hence, we provide an effective approach for the high-yield production of K. pneumoniae bioconjugate nanovaccines and guidance for uncovering glycosylation mechanisms and refining glycosylation systems.

14.
Animals (Basel) ; 14(8)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38672400

ABSTRACT

This examined the effects of Lonicera japonica extract (LJE) with different chlorogenic acid (CGA) contents on lactation performance, antioxidant status and immune function and rumen fermentation in heat-stressed high-yielding dairy cows. In total, 45 healthy Chinese Holstein high-yielding dairy cows, all with similar milk yield, parity, and days in milk were randomly allocated to 3 groups: (1) the control group (CON) without LJE; (2) the LJE-10% CGA group, receiving 35 g/(d·head) of LJE-10% CGA, and (3) the LJE-20% CGA group, receiving 17.5 g/(d·head) of LJE-20% CGA. The results showed that the addition of LJE significantly reduced RT, and enhanced DMI, milk yield, milk composition, and improved rumen fermentation in high-yielding dairy cows experiencing heat stress. Through the analysis of the serum biochemical, antioxidant, and immune indicators, we observed a reduction in CREA levels and increased antioxidant and immune function. In this study, while maintaining consistent CGA content, the effects of addition from both types of LJE are similar. In conclusion, the addition of LJE at a level of 4.1 g CGA/(d·head) effectively relieved heat stress and improved the lactation performance of dairy cows, with CGA serving as the effective ingredient responsible for its anti-heat stress properties.

15.
J Virol ; 98(5): e0025324, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38591878

ABSTRACT

Coronavirus (CoV) 3C-like protease (3CLpro) is essential for viral replication and is involved in immune escape by proteolyzing host proteins. Deep profiling the 3CLpro substrates in the host proteome extends our understanding of viral pathogenesis and facilitates antiviral drug discovery. Here, 3CLpro from porcine epidemic diarrhea virus (PEDV), an enteropathogenic CoV, was used as a model which to identify the potential 3CLpro cleavage motifs in all porcine proteins. We characterized the selectivity of PEDV 3CLpro at sites P5-P4'. We then compiled the 3CLpro substrate preferences into a position-specific scoring matrix and developed a 3CLpro profiling strategy to delineate the protein substrate landscape of CoV 3CLpro. We identified 1,398 potential targets in the porcine proteome containing at least one putative cleavage site and experimentally validated the reliability of the substrate degradome. The PEDV 3CLpro-targeted pathways are involved in mRNA processing, translation, and key effectors of autophagy and the immune system. We also demonstrated that PEDV 3CLpro suppresses the type 1 interferon (IFN-I) cascade via the proteolysis of multiple signaling adaptors in the retinoic acid-inducible gene I (RIG-I) signaling pathway. Our composite method is reproducible and accurate, with an unprecedented depth of coverage for substrate motifs. The 3CLpro substrate degradome establishes a comprehensive substrate atlas that will accelerate the investigation of CoV pathogenicity and the development of anti-CoV drugs.IMPORTANCECoronaviruses (CoVs) are major pathogens that infect humans and animals. The 3C-like protease (3CLpro) encoded by CoV not only cleaves the CoV polyproteins but also degrades host proteins and is considered an attractive target for the development of anti-CoV drugs. However, the comprehensive characterization of an atlas of CoV 3CLpro substrates is a long-standing challenge. Using porcine epidemic diarrhea virus (PEDV) 3CLpro as a model, we developed a method that accurately predicts the substrates of 3CLpro and comprehensively maps the substrate degradome of PEDV 3CLpro. Interestingly, we found that 3CLpro may simultaneously degrade multiple molecules responsible for a specific function. For instance, it cleaves at least four adaptors in the RIG-I signaling pathway to suppress type 1 interferon production. These findings highlight the complexity of the 3CLpro substrate degradome and provide new insights to facilitate the development of anti-CoV drugs.


Subject(s)
Porcine epidemic diarrhea virus , Animals , Swine , Substrate Specificity , Coronavirus 3C Proteases/metabolism , Proteome/metabolism , Humans , Proteolysis , Interferon Type I/metabolism , Coronavirus Infections/virology , Coronavirus Infections/metabolism , Coronavirus Infections/veterinary , HEK293 Cells , Viral Proteins/metabolism , Viral Proteins/genetics , Virus Replication
16.
ISA Trans ; 148: 461-476, 2024 May.
Article in English | MEDLINE | ID: mdl-38594162

ABSTRACT

Unsupervised domain adaptation alleviates the dependencies of conventional fault diagnosis methods on sufficient labeled data and strict data distributions. Nonetheless, the current domain adaptation methods only concentrate on the data distributions and ignore the feature gradient distributions, leading to some samples being misclassified due to large gradient discrepancies, thus affecting diagnosis performance. In this paper, a gradient aligned domain adversarial network (GADAN) is proposed. First, the discrepancies of the marginal and conditional distribution between the source and target domain are reduced by minimizing the joint maximum mean discrepancy. Then, a pseudo-labeling approach based on a clustering self-supervised strategy is utilized to attain high-quality pseudo-labels of target domains, and most importantly in the dimension of the data gradient, the feature gradient distributions are aligned by adversarial learning to further reduce the domain shift, even if the distributions of the two domains are close enough. Finally, experiments and engineering applications demonstrate the effectiveness and superiority of GADAN for transfer diagnosis between various working conditions or different machines.

17.
Comput Methods Programs Biomed ; 250: 108173, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38615386

ABSTRACT

BACKGROUND AND OBJECTIVE: The conventional valve stents that are cylindrical in shape will become elliptical when implanted in bicuspid aortic valve, thereby reducing the durability of the artificial valve. In this study, a new design of valve stent is presented where valve stents have elliptical cross-section at the annulus and it is expected to have better expandability and circle shape during the interaction between the stent and bicuspid aortic valve, thereby extending the durability of artificial valve. METHODS: Finite element method (FEM) is used to study the mechanical behavior of the novel valve stent in the bicuspid aortic valve. The effects of three matching relationship between the ellipticity of the stents and the ellipticity of the annulus (i.e., the ellipticity of the stent is greater than, equal to and less than the annulus ellipticity, respectively) on the mechanical behavior of stent expansion are studied. In addition, the expansion mechanical behavior of the novel valve stent at different implantation depths is also compared. RESULTS: Results indicate that novel valve stent implantation with elliptical features is superior to conventional circular valve stent. When the novel valve stent ellipticity is less than the annulus ellipticity, the ellipticity of the novel valve stent after implantation is smaller than that of the conventional circular valve stent. This indicated that the novel valve stent has better expandability and post-expansion shape, making artificial valve to have better durability. The risk of paravalvular leak after implantation is lowest when the novel valve stent ellipticity is less than annulus ellipticity. When the novel valve stent ellipticity coincides with annulus ellipticity, the aortic wall is subjected to greatest stress. With the increase of implantation depth, the stress on the novel valve stent decrease. CONCLUSIONS: This study might provide insights for improving stent design for bicuspid aortic valve.


Subject(s)
Aortic Valve , Bicuspid Aortic Valve Disease , Finite Element Analysis , Heart Valve Prosthesis , Prosthesis Design , Stents , Aortic Valve/abnormalities , Aortic Valve/surgery , Humans , Bicuspid Aortic Valve Disease/surgery , Stress, Mechanical , Heart Valve Diseases/surgery , Aortic Valve Disease/surgery
18.
Int J Biol Macromol ; 267(Pt 2): 131608, 2024 May.
Article in English | MEDLINE | ID: mdl-38621558

ABSTRACT

Amidoxime-based fiber adsorbents hold significant promise for uranium extraction. However, a notable issue is that these adsorbents primarily originate from synthetic polymer materials, which, aside from providing good mechanical support, have no other functions. In recent study, we shifted our focus to silk fiber (SF), a natural protein fiber known for its unique core-shell structure and rich amino acids. The shell layer, due to its abundant functional groups, makes it easily modifiable, while the core layer provides excellent mechanical strength. Leveraging these inherent properties, an amidoxime-based fiber adsorbent was developed. This adsorbent utilizes amino and carboxyl groups for enhanced performance synergistically. This method involves establishing uranium affinity sites on the outer sericin layer of SF via chemical initiation of graft polymerization (CIGP) and amidoximation (SF-g-PAO). The water absorption ratio of SF-g-PAO is as high as 601.16 % (DG = 97.17 %). Besides, SF-g-PAO demonstrates an exceptional adsorption capacity of 15.69 mg/g in simulated seawater, achieving a remarkable removal rate of uranyl ions at 95.06 %. It can withstand a minimum of five adsorption-elution cycles. Over a 4-week period in natural seawater, SF-g-PAO displayed an adsorption capacity of 4.95 mg/g. Furthermore, SF-g-PAO also exhibits impressive uranium removal efficiency in real nuclear wastewater, with a removal rate of 63 % in just 15 min and a final removal rate of 90 %. It is hoped that this SF-g-PAO, prepared through this straightforward method and characterized by the synergistic action of amino and carboxyl groups, can offer innovative insights into the development of uranium extraction adsorbents.


Subject(s)
Oximes , Silk , Uranium , Uranium/chemistry , Adsorption , Oximes/chemistry , Silk/chemistry , Fibroins/chemistry
19.
J Ethnopharmacol ; 329: 118149, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38580188

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate crystals play a key role in the development and recurrence of kidney stones (also known as urolithiasis); thus, inhibiting the formation of these crystals is a central focus of urolithiasis prevention and treatment. Previously, we reported the noteworthy in vitro inhibitory effects of Aspidopterys obcordata fructo oligosaccharide (AOFOS), an active polysaccharide of the traditional Dai medicine Aspidopterys obcordata Hemsl. (commonly known as Hei Gai Guan), on the growth of calcium oxalate crystals. AIM OF THE STUDY: To investigated the effectiveness and mechanism of AOFOS in treating kidney stones. MATERIALS AND METHODS: A kidney stones rats model was developed, followed by examining AOFOS transport dynamics and effectiveness in live rats. Additionally, a correlation between the polysaccharide and calcium oxalate crystals was studied by combining crystallization experiments with density functional theory calculations. RESULTS: The results showed that the polysaccharide was transported to the urinary system. Furthermore, their accumulation was inhibited by controlling their crystallization and modulating calcium ion and oxalate properties in the urine. Consequently, this approach helped effectively prevent kidney stone formation in the rats. CONCLUSIONS: The present study emphasized the role of the polysaccharide AOFOS in modulating crystal properties and controlling crystal growth, providing valuable insights into their potential therapeutic use in managing kidney stone formation.


Subject(s)
Calcium Oxalate , Crystallization , Kidney Calculi , Animals , Calcium Oxalate/chemistry , Calcium Oxalate/metabolism , Male , Rats , Kidney Calculi/prevention & control , Kidney Calculi/drug therapy , Rats, Sprague-Dawley , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Urolithiasis/drug therapy , Urolithiasis/prevention & control , Disease Models, Animal , Inulin/chemistry , Inulin/pharmacology
20.
Magn Reson Imaging ; 111: 103-112, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38685362

ABSTRACT

BACKGROUND: For patients with complete breast resection, conventional contrast-enhanced T1-weighted imaging (CE-T1WI) with frequency-selective spectral attenuated inversion recovery (SPAIR) provides limited fat suppression on the postoperative side due to the uneven skin surface, inhomogeneous tissue environment, and frequency-selective feature of the SPAIR scheme, leading to difficulties in precise diagnosis. This study aimed to investigate the image quality and performance of the Dixon method compared with SPAIR in breast high-resolution CE-T1WI for mastectomy patients. MATERIALS AND METHODS: Sixty female patients who had not performed any breast surgeries were randomly selected retrospectively as the control group. Postmastectomy female patients were enrolled to undergone high-resolution CE-T1WI with SPAIR and Dixon breast scans. Subjective scores were rated using a 5-point scale. Objective parameters, including contrast-to-noise ratio (CNR), edge sharpness, and signal uniformity were measured and calculated. The Wilcoxon rank-sum test and Kappa statistic were used. RESULTS: A total of 114 consecutive postmastectomy patients were included. Subjective scores of T1WI-SPAIR in the control group were all significantly better than those with SPAIR on the postoperative side of mastectomy patients (P < 0.01). Dixon outperformed SPAIR with significantly better subjective scores in regards to uniformity and degree of fat-suppression, anatomical structures depiction, lesion conspicuity, and axillary visibility (p < 0.05) in both post- and non-operative sides and bilateral axillary areas through the paired comparison. The objective parameters of Dixon were significantly better than those of SPAIR. CONCLUSION: The Dixon method provided better image uniformity and higher fat suppression efficiency, and showed significant advantages in delineating the anatomical structures, with better axillary and lesion visibilities, especially on the completely removed breast side.

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