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1.
Plant Physiol Biochem ; 214: 108881, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38968842

ABSTRACT

Seed germination is a critical phase for the life cycle and propagation of higher plants. This study explores the role of SlWRKY37, a WRKY transcription factor in tomato, in modulating seed germination. We discovered that SlWRKY37 expression is markedly downregulated during tomato seed germination. Through CRISPR/Cas9-mediated editing, we demonstrate that SlWRKY37 knockout enhances germination, while its overexpression results in a delay compared to the wild type. Transcriptome analysis revealed 679 up-regulated and 627 down-regulated genes in Slwrky37-CRISPR deletion mutants relative to the wild type. Gene ontology (GO) enrichment analysis indicated these differentially expressed genes are linked to seed dormancy, abscisic acid homeostasis, and protein phosphorylation pathways. Bioinformatics and biochemical assays identified SlABI5-like7 and SlLEA2 as key transcriptional targets of SlWRKY37, integral to tomato seed dormancy regulation. Additionally, SlWRKY37 was found to be post-translationally phosphorylated at Ser65, a modification crucial for its transcriptional activation. Our findings elucidate the regulatory role of SlWRKY37 in seed dormancy, suggesting its potential as a target for gene editing to reduce seed dormancy in tomato breeding programs.

2.
Inflammation ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954261

ABSTRACT

Peroxiredoxin 6 (PRDX6) has a protective effect on pulmonary epithelial cells against cigarette smoke (CS)-induced ferroptosis. This study investigates the role of PRDX6 in the development of chronic obstructive pulmonary disease (COPD) and its possibility as a target. We observed that PRDX6 was downregulated in lung tissues of COPD patients and in CS-stimulated cells. The degradation of PRDX6 could be through the lysosomal pathway. PRDX6 deficiency exacerbated pulmonary inflammation and mucus hypersecretion in vivo. Overexpression of PRDX6 in Beas-2B cells ameliorated CS-induced cell death and inflammation, suggesting its protective role against CS-induced damage. Furthermore, PRDX6 deficiency promoted ferroptosis by adding the content of iron and reactive oxygen species, while iron chelation with deferoxamine mitigated CS-induced ferroptosis, cell death, and inflammatory infiltration both in vitro and in vivo. The critical role of PRDX6 in regulating ferroptosis suggests that targeting PRDX6 or iron metabolism may represent a promising strategy for COPD treatment.

3.
Nat Nanotechnol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961247

ABSTRACT

In atomically thin van der Waals materials, grain boundaries-the line defects between adjacent crystal grains with tilted in-plane rotations-are omnipresent. When the tilting angles are arbitrary, the grain boundaries form inhomogeneous sublattices, giving rise to local electronic states that are not controlled. Here we report on epitaxial realizations of deterministic MoS2 mirror twin boundaries (MTBs) at which two adjoining crystals are reflection mirroring by an exactly 60° rotation by position-controlled epitaxy. We showed that these epitaxial MTBs are one-dimensionally metallic to a circuit length scale. By utilizing the ultimate one-dimensional (1D) feature (width ~0.4 nm and length up to a few tens of micrometres), we incorporated the epitaxial MTBs as a 1D gate to build integrated two-dimensional field-effect transistors (FETs). The critical role of the 1D MTB gate was verified to scale the depletion channel length down to 3.9 nm, resulting in a substantially lowered channel off-current at lower gate voltages. With that, in both individual and array FETs, we demonstrated state-of-the-art performances for low-power logics. The 1D epitaxial MTB gates in this work suggest a novel synthetic pathway for the integration of two-dimensional FETs-that are immune to high gate capacitance-towards ultimate scaling.

4.
Microbiol Res ; 286: 127828, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38991478

ABSTRACT

Sporulation as a typical bacterial differentiation process has been studied for decades. However, two crucial aspects of sporulation, (i) the energy sources supporting the process, and (ii) the maintenance of spore dormancy throughout sporulation, are scarcely explored. Here, we reported the crucial role of RocG-mediated glutamate catabolism in regulating mother cell lysis, a critical step for sporulation completion of Bacillus subtilis, likely by providing energy metabolite ATP. Notably, rocG overexpression resulted in an excessive ATP accumulation in sporulating cells, leading to adverse effects on future spore properties, e.g. increased germination efficiency, reduced DPA content, and lowered heat resistance. Additionally, we revealed that Ald-mediated alanine metabolism was highly related to the inhibition of premature germination and the maintenance of spore dormancy during sporulation, which might be achieved by decreasing the typical germinant L-alanine concentration in sporulating environment. Our data inferred that sporulation of B. subtilis was a highly orchestrated biological process requiring a delicate balance in diverse metabolic pathways, hence ensuring both the completion of sporulation and production of high-quality spores.

5.
World J Clin Cases ; 12(18): 3351-3359, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38983394

ABSTRACT

BACKGROUND: In rhinoplasty, calcification around silicone implants is frequently observed in the tip dorsum (TD) area. Additionally, based on a review of various literature, it is presumed that calcification in silicone implants occurs due to both inflammatory chemical reactions and physical friction against the tissue. The calcification of nasal silicone implants not only results in the functional loss of the implants, but also leads to material deformation. However, there is a lack of research on calcification of nasal silicone implants in the current literature. AIM: To elucidate various clinical characteristics of calcification around nasal silicone implants, using histological and radiological analysis. METHODS: This study analyzed data from 16 patients of calcified nasal implants, who underwent revision rhinoplasty for various reasons after undergoing augmentation rhinoplasty with silicone implants. The collected data included information on implant duration, implant types, location of calcification, presence of inflammatory reactions, and computed tomography (CT) scans. RESULTS: The most common location of calcification, as visually analyzed, was in the TD area, accounting for 56%. Additionally, the analysis of CT scans revealed a trend of increasing Hounsfield Unit values for calcification with the duration of implantation, although this trend was not statistically significant (P = 0.139). CONCLUSION: Our study shows that reducing the frequency of calcification may be achievable by using softer silicone implants and by minimizing the damage to perioperative tissues.

6.
Int Orthop ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987511

ABSTRACT

PURPOSE: To compare the clinical efficacy and prognosis differences between conservative treatment and surgical treatment in patients with non-serious neurologically intact pyogenic spondylitis (Nsi-Nsni-PS), and to provide theoretical reference for the clinical treatment of Nsi-Nsni-PS patients. METHODS: A retrospective analysis was conducted on 112 cases of Nsi-Nsni-PS patients treated in our hospital from June 2016 to June 2021. According to different treatment methods, they were divided into conservative treatment group (53 cases) and surgical treatment group (59 cases). The general data, laboratory tests, imaging examinations, length of hospital stay, duration of antibiotic use, VAS for pain before and after treatment, ODI, local kyphotic angle correction of diseased vertebrae, and recurrence rate were collected and analyzed in both groups. SPSS 26.0 statistical software was used for analysis. Measurement data were expressed as mean ± standard deviation, and independent sample t-test or rank sum test was used for comparison between groups, while variance analysis was used for intra-group comparison. Count data were expressed as number (%) and compared between groups using chi-square test or Fisher's exact test. Mann-Whitney U test was used to evaluate the changes in local kyphotic angle between the two groups. A p value < 0.05 was considered statistically significant. RESULTS: There were no significant differences in general data and imaging characteristics between the two groups (P > 0.05); there were no statistically significant differences in the positive culture rate of pathogens, length of hospital stay, duration of antibiotic use, treatment complications, WBC, CRP, ESR levels at admission and discharge, VAS and ODI at admission and last follow-up between the two groups (P > 0.05). The WBC and CRP levels of patients in the conservative group at discharge were lower than those in the surgical group (P < 0.05), and there was no significant difference in the decrease in inflammatory indicators (WBC, CRP, ESR) between the two groups (P > 0.05). By the last follow-up, the neurological function of patients in both groups had significantly improved compared to admission (P < 0.05), with 12 out of 15 ASIA grade D patients in the conservative group recovering to grade E, and 21 out of 25 grade D patients in the surgical group recovering to grade E, with no worsening of neurological function in either group. The differences in VAS and ODI scores at the last follow-up compared to before treatment were statistically significant in both groups (P < 0.05), and all patients regained normal activity. Compared with before treatment, the correction degree of local kyphotic angle in the surgical group at the last follow-up was 0.93 ± 4.94°, slightly higher than that in the conservative group (-0.83 ± 3.37°), and the difference was statistically significant(P < 0.05). CONCLUSIONS: During our follow-up, we found that both conservative and surgical treatments achieved satisfactory clinical outcomes in patients with Nsi-Nsni-PS. Compared to conservative treatment, surgical intervention did not demonstrate significant advantages in reducing hospitalization time and antibiotic usage duration, increasing pathogen culture positivity rate, lowering treatment complications, or controlling recurrence. However, surgical intervention showed superiority in correcting the local kyphotic angle of spinal lesions, albeit with relatively increased surgical trauma, risks, and treatment costs. At the last follow-up, the surgical group did not exhibit better long-term efficacy. Therefore, when formulating clinical treatment strategies for patients with Nsi-Nsni-PS, it may be preferable to prioritize conservative treatment, supplemented by the use of sensitive or empiric antibiotics for infection management, to improve patient prognosis.

7.
Wideochir Inne Tech Maloinwazyjne ; 19(1): 1-10, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38974765

ABSTRACT

Introduction: The Pfannenstiel incision is often used in gynecological Cesarean section; however, there is limited research on the use of the Pfannenstiel incision for specimen extraction in laparoscopic surgery for the treatment of colorectal cancer. Aim: To evaluate the safety of using the Pfannenstiel incision for specimen extraction in laparoscopic surgery for colorectal cancer patients. Material and methods: PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and WanFangData were searched for studies published up to March 10, 2023; a random-effects model (RCT) and a fixed-effect model were used to evaluate the safety. Operative time, length of extraction skin incision, overall complications, superficial wound infection, organ/space surgical site infection and incisional hernia were evaluated. Results: A total of 5 studies were included in this research. There were no significant advantages in operation time, length of the incision, overall complications, superficial wound infection and organ/space surgical site in the Pfannenstiel group compared to the no Pfannenstiel group. However, the Pfannenstiel incision has a tendency to increase the length of the incision (SMD = 0.05; 95% CI = -0.22 to 0.33; p = 0.71) and the results of the remaining five (operative time,overall complications,incisional hernia, incisional infection and organ/space surgical site infection) are slightly skewed toward the Pfannenstiel incision. It is worth mentioning that incisional hernia (IH) may have an advantage in the Pfannenstiel group compared to the no Pfannenstiel group. Four studies were not at clear risk of bias and two studies were at risk of bias. Conclusions: Our study concludes that the Pfannenstiel incision has a good safety record and it is a good option for extracting specimens during laparoscopic surgery for colon cancer. The Pfannenstiel incision used for laparoscopic surgical specimen extraction has a significantly lower incidence of incisional hernia over no Pfannenstiel.

8.
Int J Biol Macromol ; 275(Pt 1): 133568, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38969033

ABSTRACT

This paper initially examines the feasibility and effectiveness on interfacial adhesion of composites when grafting nanoparticle-structured polydopamine (PDA) and chitosan around carbon fiber periphery. The resulting interfacial shear strength was maximized as 92.3 MPa, delivering 50.1 % and 15.7-16.2 % gains over those of control fiber and only polydopamine nanospheres (PDANPs) or only chitosan modified fiber composites. Measuring surface morphology and thermal stability of fibers found that abundant PDANPs well adhered with the help of chitosan, highlighting nanoscale size effects and intrinsic adhesiveness of PDA. Under good wettability, rich and dense interfacial interactions (covalent and hydrogen bond, electrostatic interaction, and π conjugation) caused by PDANPs/chitosan coating provides impetus for effective stress transfer. Additionally, the stable "soft-rigid" combination of chitosan and PDANPs adds the efficiency of crack passivation. As such, it is hoped that this work could fully explore the possibility of PDA geometry in interphase engineering of fiber composites.

9.
Sci Rep ; 14(1): 15735, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977721

ABSTRACT

The influence of precipitated nanophases on the mechanical properties of Fe-based amorphous nanocrystalline alloys is an urgent issue to be explored. Two amorphous nanocrystalline alloys, i.e., (Fe0.9Ni0.1)86B14 and (Fe0.7Ni0.3)86B14 containing nanophase of the body-centered cubic and face-centered cubic structures, respectively, were selected to investigate the effect of the structure and volume fraction of nanophase on their mechanical properties. The results of nanoindentation experiments and the calculation of the volume and size of the shear transition zone reveal that the two alloys show different mechanical properties. When the volume fraction of the nanophase in (Fe0.9Ni0.1)86B14 is larger than 50%, the elastic modulus is increased suddenly and the volume and size of the shear transition zone is decreased dramatically, while no dramatic change occurs in (Fe0.7Ni0.3)86B14. Moreover, it was found by using molecular dynamics simulations that the main reason for these abnormal mechanical properties is the change of cluster type in the system due to the incorporation of nanophases with different structures.

10.
Medicine (Baltimore) ; 103(28): e38860, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996164

ABSTRACT

The purpose of the current study was to analyze whether aortic calcification had impact on the anastomotic leakage (AL) after rectal cancer (RC) surgery. We collected patients' information from January 2011 to January 2020 in a single teaching hospital. Preoperative computed tomography images were obtained. Abdominal aortic calcification (AAC), superior mesenteric aortic calcification, and inferior mesenteric aortic calcification were recorded. The difference of AL and grade C AL was calculated. A total of 2412 RC patients were included in this study. Ninety-seven (4.0%) RC patients experienced AL and 47 (1.9%) RC patients experienced grade C AL. The amount of AAC, superior mesenteric aortic calcification, and inferior mesenteric aortic calcification was 1546 (64.1%), 128 (5.3%), and 31 (1.3%). The AL group had higher portion of AAC (P = .019) than the no AL group, and the grade C AL group had higher portion of AAC (P = .016) than the no grade C AL group. In univariate logistic regression analysis, AAC was a significant potential factor for AL (P = .021, OR = 1.739, 95% CI = 1.088-2.779) and grade C AL (P = .019, OR = 2.339, 95% CI = 1.115-4.986). However, in multivariate logistic regression, AAC was not an independent predictive factor for AL (P = .157, OR = 1.443, 95% CI = 0.871-2.358) or grade C AL (P = .064, OR = 2.055, 95% CI = 0.960-4.399). AAC was associated with higher amount of AL and grade C AL, however, AAC was not an independent predictive factor for AL or grade C AL.


Subject(s)
Anastomotic Leak , Rectal Neoplasms , Vascular Calcification , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Male , Female , Anastomotic Leak/etiology , Anastomotic Leak/epidemiology , Middle Aged , Aged , Vascular Calcification/diagnostic imaging , Retrospective Studies , Aorta, Abdominal/surgery , Aorta, Abdominal/diagnostic imaging , Tomography, X-Ray Computed , Aortic Diseases/surgery , Risk Factors
11.
Int J Biol Macromol ; : 133814, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38996888

ABSTRACT

The incidence of esophageal cancer continues to increase worldwide. Current therapeutic approaches have limited efficacy, so in order to search for better markers of the disease, it is necessary to further elucidate its molecular pathogenesis. Regulation of gene expression by long non-coding Rnas plays a role in many diseases, however the role in esophageal cancer is unclear. The aim of this study was to elucidate the role and regulatory mechanism of long non-coding RNA NRSN2-AS1 in the progression of esophageal cancer. By real-time quantitative PCR, immunohistochemistry, RNA interference, western blotting, and double luciferase reporter gene analysis, we found that NRSN2-AS1 was up-regulated in esophageal cancer tissues and cell lines, and was closely related to disease stage and prognosis. Functional studies have shown that the silencing of NRSN2-AS1 inhibits the proliferation of esophageal cancer cells, induces apoptosis, and prevents cell migration and invasion. In mouse models, NRSN2-AS1 also promoted tumor growth. The transcription factor TCFL5 upregulates the transcription of NRSN2-AS1, which acts as a sponge for microRNA(miR)-874-5p, thereby upregulating the expression of the oncogene RELT. Activation of the NRSN2-AS1/miR-874-5p/RELT regulatory axis was validated in vivo.

12.
Int J Mol Sci ; 25(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39000355

ABSTRACT

Postmenopausal osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation, presents substantial health implications. In this study, we investigated the role of black goat extract (BGE), derived from a domesticated native Korean goat, estrogen-like activity, and osteoprotective effects in vitro. BGE's mineral and fatty acid compositions were analyzed via the ICP-AES method and gas chromatography-mass spectrometry, respectively. In vitro experiments were conducted using MCF-7 breast cancer cells, MC3T3-E1 osteoblasts, and RAW264.7 osteoclasts. BGE exhibits a favorable amount of mineral and fatty acid content. It displayed antimenopausal activity by stimulating MCF-7 cell proliferation and augmenting estrogen-related gene expression (ERα, ERß, and pS2). Moreover, BGE positively impacted osteogenesis and mineralization in MC3T3-E1 cells through Wnt/ß-catenin pathway modulation, leading to heightened expression of Runt-related transcription factor 2, osteoprotegerin, and collagen type 1. Significantly, BGE effectively suppressed osteoclastogenesis by curtailing osteoclast formation and activity in RAW264.7 cells, concurrently downregulating pivotal signaling molecules, including receptor activator of nuclear factor κ B and tumor necrosis factor receptor-associated factor 6. This study offers a shred of preliminary evidence for the prospective use of BGE as an effective postmenopausal osteoporosis treatment.


Subject(s)
Cell Differentiation , Goats , Osteoblasts , Osteoclasts , Osteogenesis , Animals , Mice , RAW 264.7 Cells , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteogenesis/drug effects , Cell Differentiation/drug effects , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteoclasts/cytology , Humans , Estrogens/pharmacology , Cell Proliferation/drug effects , Wnt Signaling Pathway/drug effects , MCF-7 Cells , Tissue Extracts/pharmacology
13.
Sensors (Basel) ; 24(13)2024 Jul 07.
Article in English | MEDLINE | ID: mdl-39001188

ABSTRACT

Since light propagation in a multimode fiber (MMF) exhibits visually random and complex scattering patterns due to external interference, this study numerically models temperature and curvature through the finite element method in order to understand the complex interactions between the inputs and outputs of an optical fiber under conditions of temperature and curvature interference. The systematic analysis of the fiber's refractive index and bending loss characteristics determined its critical bending radius to be 15 mm. The temperature speckle atlas is plotted to reflect varying bending radii. An optimal end-to-end residual neural network model capable of automatically extracting highly similar scattering features is proposed and validated for the purpose of identifying temperature and curvature scattering maps of MMFs. The viability of the proposed scheme is tested through numerical simulations and experiments, the results of which demonstrate the effectiveness and robustness of the optimized network model.

14.
J Imaging Inform Med ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980623

ABSTRACT

Malposition of a nasogastric tube (NGT) can lead to severe complications. We aimed to develop a computer-aided detection (CAD) system to localize NGTs and detect NGT malposition on portable chest X-rays (CXRs). A total of 7378 portable CXRs were retrospectively retrieved from two hospitals between 2015 and 2020. All CXRs were annotated with pixel-level labels for NGT localization and image-level labels for NGT presence and malposition. In the CAD system, DeepLabv3 + with backbone ResNeSt50 and DenseNet121 served as the model architecture for segmentation and classification models, respectively. The CAD system was tested on images from chronologically different datasets (National Taiwan University Hospital (National Taiwan University Hospital)-20), geographically different datasets (National Taiwan University Hospital-Yunlin Branch (YB)), and the public CLiP dataset. For the segmentation model, the Dice coefficients indicated accurate delineation of the NGT course (National Taiwan University Hospital-20: 0.665, 95% confidence interval (CI) 0.630-0.696; National Taiwan University Hospital-Yunlin Branch: 0.646, 95% CI 0.614-0.678). The distance between the predicted and ground-truth NGT tips suggested accurate tip localization (National Taiwan University Hospital-20: 1.64 cm, 95% CI 0.99-2.41; National Taiwan University Hospital-Yunlin Branch: 2.83 cm, 95% CI 1.94-3.76). For the classification model, NGT presence was detected with high accuracy (area under the receiver operating characteristic curve (AUC): National Taiwan University Hospital-20: 0.998, 95% CI 0.995-1.000; National Taiwan University Hospital-Yunlin Branch: 0.998, 95% CI 0.995-1.000; CLiP dataset: 0.991, 95% CI 0.990-0.992). The CAD system also detected NGT malposition with high accuracy (AUC: National Taiwan University Hospital-20: 0.964, 95% CI 0.917-1.000; National Taiwan University Hospital-Yunlin Branch: 0.991, 95% CI 0.970-1.000) and detected abnormal nasoenteric tube positions with favorable performance (AUC: 0.839, 95% CI 0.807-0.869). The CAD system accurately localized NGTs and detected NGT malposition, demonstrating excellent potential for external generalizability.

15.
Anal Chem ; 96(28): 11603-11610, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38953495

ABSTRACT

Long noncoding RNAs (lncRNAs) act as the dynamic regulatory molecules that control the expression of genes and affect numerous biological processes, and their dysregulation is associated with tumor progression. Herein, we develop a fluorescent light-up aptasensor to simultaneously measure multiple lncRNAs in living cells and breast tissue samples based on the DNAzyme-mediated cleavage reaction and transcription-driven synthesis of light-up aptamers. When target lncRNAs are present, they can be recognized by template probes to form the active DNAzyme structures, initiating the T4 PNK-catalyzed dephosphorylation-triggered extension reaction to generate double-strand DNAs with the T7 promoter sequences. The corresponding T7 promoters can initiate the transcription amplification catalyzed by the T7 RNA polymerase to generate abundant Broccoli aptamers and malachite green aptamers, which can bind DFHBI-1T and MG to generate strong fluorescence signals. Taking advantage of the good selectivity of DNAzyme-mediated cleavage of lncRNAs, high amplification efficiency of T7 transcription-driven amplification reaction, and bright fluorescence of the RNA aptamer-fluorophore complex, this method exhibits high sensitivity with a detection limit of 21.4 aM for lncRNA HOTAIR and 18.47 aM for lncRNA MALAT1, and it can accurately measure multiple lncRNAs in both tumor cell lines and breast tissue samples, providing a powerful paradigm for biomedical research and early clinic diagnostics.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , DNA, Catalytic , Fluorescent Dyes , RNA, Long Noncoding , DNA, Catalytic/chemistry , DNA, Catalytic/metabolism , RNA, Long Noncoding/analysis , RNA, Long Noncoding/metabolism , RNA, Long Noncoding/genetics , Humans , Aptamers, Nucleotide/chemistry , Fluorescent Dyes/chemistry , Limit of Detection , Fluorescence
16.
World J Gastrointest Oncol ; 16(6): 2697-2715, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994159

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC. AIM: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC. METHODS: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database. RESULTS: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 µmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO). CONCLUSION: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 µmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect.

17.
World J Clin Cases ; 12(19): 3800-3806, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38994310

ABSTRACT

BACKGROUND: Hypocalcemia is highly common in hospitalized patients, especially in those with trauma, On the other hand, abnormal calcium metabolism is an important metabolic challenge; however, it is often neglected and untreated, and certain factors may induce serious neurological and cardiovascular complications. AIM: To retrospectively analyze the impact of hypocalcemia on the prognosis of patients with multiple traumas. METHODS: The study was conducted from January 2020 to December 2021. Ninety-nine patients with multiple injuries were treated at the critical care medicine department of Fuyang People's Hospital. The selected indicators included sex, age, and blood calcium and hematocrit levels. Many indicators were observed, including within 24 h of hospitalization, and the prognosis was collected after 28 d. Based on the blood calcium levels, the patients were divided into the following two groups: Normocalcemia and hypocalcemia. Of the 99 patients included, 81 had normocalcemia, and 18 had hypocalcemia. Separate experiments were conducted for these two groups. RESULTS: There was an association between serum calcium levels and the prognosis of patients with polytrauma. CONCLUSION: Clinically, the prognosis of patients with multiple traumas can be preliminarily evaluated based on serum calcium levels.

18.
Nutr Res ; 128: 14-23, 2024 May 29.
Article in English | MEDLINE | ID: mdl-39002358

ABSTRACT

Sesamolin, a lignan isolated from sesame oils, has been found to possess neuroprotective, anticancer, and free radical scavenging properties. We hypothesized that sesamolin could stimulate the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2) and inhibit adipocyte differentiation of preadipocytes. The objective of this study was to investigate effects of sesamolin on adipocyte differentiation and its underlying molecular mechanisms. In this study, we determined the effects of treatment with 25 to 100 µM sesamolin on adipogenesis in cell culture systems. Sesamolin inhibited lipid accumulation and suppressed the expression of adipocyte markers during adipocyte differentiation of C3H10T1/2, 3T3-L1, and primary preadipocytes. Mechanism studies revealed that sesamolin increased Nrf2 protein expression without inducing its mRNA, leading to an increase in the expression of Nrf2 target genes such as heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 (Nqo1) in C3H10T1/2 adipocytes and mouse embryonic fibroblasts. These effects were significantly attenuated in Nrf2 knockout (KO) mouse embryonic fibroblasts, indicating that effects of sesamolin were dependent on Nrf2. In H1299 human lung cancer cells with KO of Kelch like-ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, sesamolin failed to further increase Nrf2 protein expression. However, upon reexpressing Keap1 in Keap1 KO cells, the ability of sesamolin to elevate Nrf2 protein expression was restored, highlighting the crucial role of Keap1 in sesamolin-induced Nrf2 activation. Taken together, these findings show that sesamolin can inhibit adipocyte differentiation through Keap1-mediated Nrf2 activation.

19.
IEEE Trans Cybern ; PP2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012746

ABSTRACT

This article introduces an adaptive dynamic event-triggered technique for addressing the output tracking control problem of uncertain switched nonlinear systems with prescribed performance. First, a switching dynamic event-triggered mechanism (SDETM) is established to alleviate network burden and conserve computational resources. A notable aspect is the inclusion of asynchronous switching between the switching subsystems and controllers. Second, a state-dependent switching law ensuring a dwell-time constraint is designed, which avoids the frequent switching phenomenon within any finite time interval. Third, an SDETM and an adaptive dynamic event-triggered controller are developed to confine the output tracking error within predefined decaying boundaries, while ensuring that all the signals of the closed-loop switched system remain within bounded regions. Finally, the validity and applicability of the developed control scheme are demonstrated through a one-link manipulator example.

20.
Nat Commun ; 15(1): 5927, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009678

ABSTRACT

Duchenne muscular dystrophy (DMD) affecting 1 in 3500-5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient's DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.


Subject(s)
Adenine , CRISPR-Cas Systems , Disease Models, Animal , Dystrophin , Exons , Gene Editing , Muscular Dystrophy, Duchenne , Animals , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/therapy , Dystrophin/genetics , Dystrophin/metabolism , Exons/genetics , Humans , Male , Gene Editing/methods , Mice , Adenine/metabolism , Muscle, Skeletal/metabolism , Dependovirus/genetics , Genetic Therapy/methods
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