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1.
J Sci Food Agric ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953326

ABSTRACT

BACKGROUND: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. RESULTS: KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1ß (764.81 ng mL-1), interleukin-6 (1.06 ng mL-1) and tumor necrosis factor-α (4440.45 ng mL-1). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 µg mL-1; superoxide dismutase: 0.589 µg mL-1) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 µg mL-1). CONCLUSION: Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.

2.
Quant Imaging Med Surg ; 14(7): 4936-4949, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39022281

ABSTRACT

Background: Malignant cerebral edema (MCE), a potential complication following endovascular thrombectomy (EVT) in the treatment of acute ischemic stroke (AIS), can result in significant disability and mortality. This study aimed to develop a nomogram model based on the hyperattenuated imaging marker (HIM), characterized by hyperattenuation on head noncontrast computed tomography (CT) immediately after thrombectomy, to predict MCE in patients receiving EVT. Methods: In this retrospective cohort study, we selected 151 patients with anterior circulation large-vessel occlusion who received endovascular treatment. The patients were randomly allocated into training (n=121) and test (n=30) cohorts. HIM was used to extract radiomics characteristics. Conventional clinical and radiological features associated with MCE were also extracted. A model based on extreme gradient boosting (XGBoost) machine learning using fivefold cross-validation was employed to acquire radiomics and clinical features. Based on HIM, clinical and radiological signatures were used to construct a prediction nomogram for MCE. Subsequently, the signatures were merged through logistic regression (LR) analysis in order to create a comprehensive clinical radiomics nomogram. Results: A total of 28 patients out of 151 (18.54%) developed MCE. The analysis of the receiver operating characteristic curve indicated an area under the curve (AUC) of 0.999 for the prediction of MCE in the training group and an AUC of 0.938 in the test group. The clinical and radiomics nomogram together showed the highest accuracy in predicting outcomes in both the training and test groups. Conclusions: The novel nomogram, which combines clinical manifestations and imaging findings based on postinterventional HIM, may serve as a predictor for MCE in patients experiencing AIS after EVT.

3.
J Sci Food Agric ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39056251

ABSTRACT

BACKGROUND: Chinese giant salamander protein hydrolysates (CGSPH) are beneficial to human health as a result of their high content of amino acids and peptides. However, the formation of bitter peptides in protein hydrolysates (PHs) would hinder their application in food industry. The ultrasound assisted wet-heating Maillard reaction (MR) is an effective way to improve the flavor of PHs. Thus, the effect of ultrasonic assisted wet-heating MR on the structure and flavor of CGSPH was investigated in the present study. RESULTS: The results indicated that the ultrasound assisted wet-heating MR products (MRPs) exhibited a higher degree of graft and more significant changes in the secondary and tertiary structures of CGSPH compared to traditional wet-heating MRPs. Moreover, ultrasound assisted wet-heating MR could significantly increase the content of small molecule peptides and reduce the content of free amino acids of CGSPH, which resulted in more significant changes in flavor characteristics. The changed in flavor properties after MR (especially ultrasound assisted wet-heating MRPs) were mainly manifested by a significant reduction in bitterness, as well as a significant increase in the content of aromatic aldehyde ester compounds such as furan-2-carbaldehyde, butanal, benzaldehyde, furfural, etc. CONCLUSIONS: Ultrasound assisted wet-heating MR between CGSPH and xylose could be a promising way to improve the sensory characteristics of CGSPH. © 2024 Society of Chemical Industry.

4.
Foods ; 13(14)2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39063275

ABSTRACT

Near-infrared spectroscopy (NIR) has become an essential tool for non-destructive analysis in various fields, including aquaculture. This study presents a pioneering application of portable NIR spectrometers to analyze glycogen content in the gonadal tissues of the Pacific oyster (Crassostrea gigas), marking the first instance of developing quantitative models for glycogen in tetraploid C. gigas. The research also provides a comparative analysis with models for diploid and triploid oysters, underscoring the innovative use of portable NIR technology in aquaculture. Two portable NIR spectrometers were employed: the Micro NIR 1700 (908-1676 nm) and the Micro PHAZIR RX (1624-2460 nm). Near-infrared spectra were acquired from the gonadal tissues of diploid, triploid, and tetraploid C. gigas. Quantitative models for glycogen content were developed and validated using cross-validation methods. Additionally, qualitative models for different ploidies and genders were established. For the Micro NIR 1700, the cross-validation correlation coefficients (Rcv) and cross-validation relative predictive errors (RPDcv) for glycogen were 0.949 and 3.191 for diploids, 0.915 and 2.498 for triploids, and 0.902 and 2.310 for tetraploids. The Micro PHAZIR RX achieved Rcv and RPDcv values of 0.781 and 2.240 for diploids, 0.839 and 2.504 for triploids, and 0.717 and 1.851 for tetraploids. The Micro NIR 1700 demonstrated superior quantitative performance, with RPD values exceeding 2, indicating its effectiveness in predicting glycogen content across different ploidy levels. Qualitative models showed a performance index of 91.6 for diploid and 95 for tetraploid genders using the Micro NIR 1700, while the Micro PHAZIR RX achieved correct identification rates of 99.79% and 100% for diploid and tetraploid genders, respectively. However, differentiation of ploidies was less successful with both instruments. This study's originality lies in establishing the first quantitative models for glycogen content in tetraploid C. gigas using portable NIR spectrometers, highlighting the significant advancements in non-destructive glycogen analysis. The applicability of these findings is substantial for oyster breeding programs focused on enhancing meat quality traits. These models provide a valuable phenotyping tool for selecting oysters with optimal glycogen content, demonstrating the practical utility of portable NIR technology in aquaculture.

5.
Front Microbiol ; 15: 1407800, 2024.
Article in English | MEDLINE | ID: mdl-38939188

ABSTRACT

The iron transport system plays a crucial role in the extracellular electron transfer process of Shewanella sp. In this study, we fabricated a vertically oriented α-Fe2O3 nanoarray on carbon cloth to enhance interfacial electron transfer in Shewanella putrefaciens CN32 microbial fuel cells. The incorporation of the α-Fe2O3 nanoarray not only resulted in a slight increase in flavin content but also significantly enhanced biofilm loading, leading to an eight-fold higher maximum power density compared to plain carbon cloth. Through expression level analyses of electron transfer-related genes in the outer membrane and core genes in the iron transport system, we propose that the α-Fe2O3 nanoarray can serve as an electron mediator, facilitating direct electron transfer between the bacteria and electrodes. This finding provides important insights into the potential application of iron-containing oxide electrodes in the design of microbial fuel cells and other bioelectrochemical systems, highlighting the role of α-Fe2O3 in promoting direct electron transfer.

6.
Molecules ; 29(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38893545

ABSTRACT

Tetraploid oysters are artificially produced oysters that do not exist in nature. The successful breeding of 100% triploid oysters resolved the difficulties of traditional drug-induced triploids, such as the presence of drug residues and a low triploid induction rate. However, little is known concerning the biochemical composition and nutrient contents of such tetraploids. Therefore, we investigated compositional differences among diploid, triploid, and tetraploid Crassostrea gigas as well as between males and females of diploids and tetraploids. The findings indicated that glycogen, EPA, ∑PUFA, and omega-3 contents were significantly higher in triploid oysters than in diploids or tetraploids; tetraploid oysters had a significantly higher protein content, C14:0, essential amino acid, and flavor-presenting amino acid contents than diploids or triploids. For both diploid and tetraploids, females had significantly higher levels of glutamate, methionine, and phenylalanine than males but lower levels of glycine and alanine. In addition, female oysters had significantly more EPA, DHA, omega-3, and total fatty acids, a result that may be due to the fact that gonadal development in male oysters requires more energy to sustain growth, consumes greater amounts of nutrients, and accumulates more proteins. With these results, important information is provided on the production of C. gigas, as well as on the basis and backing for the genetic breeding of oysters.


Subject(s)
Amino Acids , Crassostrea , Diploidy , Fatty Acids , Tetraploidy , Triploidy , Animals , Crassostrea/genetics , Crassostrea/metabolism , Amino Acids/metabolism , Fatty Acids/metabolism , Fatty Acids/analysis , Female , Male
7.
Opt Lett ; 49(11): 3255-3258, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824377

ABSTRACT

A high-peak-power, widely tunable range long-wave infrared optical parametric oscillator (OPO) based on the BaGa4Se7 (BGSe) crystal is demonstrated in this Letter. Pumped by a 1064 nm Nd:YAG laser, a high-peak-power of 0.15 MW was achieved at 9.8 µm with a pulse width of 5.0 ns. At 11.0 µm, a high beam quality of M2x = 4.1 and M2y = 3.3 was achieved. By rotating the BGSe crystal, a broad tuning range of 6.7-13.9 µm was realized. Furthermore, a theoretical analysis was conducted to elucidate the reasons behind the improvement in beam quality in the x-direction as the wavelength of the idler wave increases.

8.
Food Res Int ; 186: 114410, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729706

ABSTRACT

Protein and lipid are two major components that undergo significant changes during processing of aquatic products. This study focused on the protein oxidation, protein conformational states, lipid oxidation and lipid molecule profiling of salted large yellow croaker during storage, and their correlations were investigated. The degree of oxidation of protein and lipid was time-dependent, leading to an increase in carbonyl content and surface hydrophobicity, a decrease in sulfhydryl groups, and an increase in conjugated diene, peroxide value and thiobarbituric acid reactive substances value. Oxidation caused protein structure denaturation and aggregation during storage. Lipid composition and content changed dynamically, with polyunsaturated phosphatidylcholine (PC) was preferentially oxidized compared to polyunsaturated triacylglycerol. Correlation analysis showed that the degradation of polyunsaturated key differential lipids (PC 18:2_20:5, PC 16:0_22:6, PC 16:0_20:5, etc.) was closely related to the oxidation of protein and lipid. The changes in protein conformation and the peroxidation of polyunsaturated lipids mutually promote each other's oxidation process.


Subject(s)
Fish Proteins , Food Storage , Oxidation-Reduction , Perciformes , Animals , Perciformes/metabolism , Fish Proteins/chemistry , Lipid Peroxidation , Hydrophobic and Hydrophilic Interactions , Lipids/chemistry , Protein Conformation , Thiobarbituric Acid Reactive Substances/analysis , Seafood/analysis
9.
J Endocr Soc ; 8(6): bvae061, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38650712

ABSTRACT

Introduction: Pheochromocytomas (PCC) and paragangliomas (PGL) (collectively PPGL) are a type of rare hypervascular neuroendocrine tumors that are very challenging to treat. This study aimed to determine the efficacy and safety of the multi-tyrosine kinase inhibitor anlotinib for the treatment of locally advanced or metastatic (LA/M) PPGL. Methods: A total of 37 eligible patients with unresectable or progressive LA/M PPGL were enrolled. Of them, 27 patients received anlotinib alone (n = 19) or in combination (n = 8) with radionuclide therapies, including peptide receptor radionuclide therapy (PRRT) and iodine 131 meta-iodobenzylguanidine (131I-MIBG). The primary endpoints included objective response rate (ORR), defined as partial response (PR) or complete response (CR), and disease-control rate, defined as PR, CR, or stable disease (SD). The secondary endpoints were progression-free survival (PFS), duration of response, and drug safety. Results: In the efficacy evaluation for all 27 patients, the ORR was 44.44% (95% CI: 24.4%-64.5%) and disease-control rate was 96.29% (95% CI: 88.7%-100%). Twelve cases (44.44%) achieved PR, 14 (51.85%) SD. The median PFS was 25.2 months (95% CI: 17.2 months to not reached). PFS was shorter in the anlotinib monotherapy group than in the group receiving anlotinib in combination with radionuclide therapy (P = .2). There were no serious treatment-related AEs. Conclusion: Anlotinib monotherapy or in combination with radionuclide therapies shows promising efficacy and safety for the treatment of LA/M PCC and PGL. Multi-tyrosine kinase inhibitors might represent a novel therapeutic strategy for patients with PPGL; however, large-scale prospective randomized, blinded, controlled clinical research studies are required.

11.
Food Chem ; 449: 139302, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38608610

ABSTRACT

In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.


Subject(s)
Hot Temperature , Sea Cucumbers , Animals , Sea Cucumbers/chemistry , Flavoring Agents/chemistry , Flavoring Agents/metabolism , Protein Hydrolysates/chemistry , Taste , Hydrolysis , Peptide Hydrolases/chemistry , Peptide Hydrolases/metabolism , Ultrasonic Waves
12.
PeerJ ; 12: e17304, 2024.
Article in English | MEDLINE | ID: mdl-38680887

ABSTRACT

The MYB gene family exerts significant influence over various biological processes and stress responses in plants. Despite this, a comprehensive analysis of this gene family in pumpkin remains absent. In this study, the MYB genes of Cucurbita moschata were identified and clustered into 33 groups (C1-33), with members of each group being highly conserved in terms of their motif composition. Furthermore, the distribution of 175 CmoMYB genes across all 20 chromosomes was found to be non-uniform. Examination of the promoter regions of these genes revealed the presence of cis-acting elements associated with phytohormone responses and abiotic/biotic stress. Utilizing quantitative real-time polymerase chain reaction (qRT-PCR), the expression patterns of 13 selected CmoMYB genes were validated, particularly in response to exogenous phytohormone exposure and various abiotic stressors, including ABA, SA, MeJA, and drought treatments. Expression analysis in different tissues showed that CmoMYB genes are expressed at different levels in different tissues, suggesting that they are functionally divergent in regulating growth and abiotic stresses. These results provide a basis for future studies to characterize the function of the MYB gene family under abiotic stresses in pumpkins.


Subject(s)
Cucurbita , Gene Expression Regulation, Plant , Multigene Family , Stress, Physiological , Cucurbita/genetics , Multigene Family/genetics , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Growth Regulators/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Genes, myb , Promoter Regions, Genetic/genetics , Phylogeny , Genome-Wide Association Study , Genome, Plant/genetics
13.
Nature ; 628(8006): 180-185, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38480886

ABSTRACT

The gut microbiome has major roles in modulating host physiology. One such function is colonization resistance, or the ability of the microbial collective to protect the host against enteric pathogens1-3, including enterohaemorrhagic Escherichia coli (EHEC) serotype O157:H7, an attaching and effacing (AE) food-borne pathogen that causes severe gastroenteritis, enterocolitis, bloody diarrhea and acute renal failure4,5 (haemolytic uremic syndrome). Although gut microorganisms can provide colonization resistance by outcompeting some pathogens or modulating host defence provided by the gut barrier and intestinal immune cells6,7, this phenomenon remains poorly understood. Here, we show that activation of the neurotransmitter receptor dopamine receptor D2 (DRD2) in the intestinal epithelium by gut microbial metabolites produced upon dietary supplementation with the essential amino acid L-tryptophan protects the host against Citrobacter rodentium, a mouse AE pathogen that is widely used as a model for EHEC infection8,9. We further find that DRD2 activation by these tryptophan-derived metabolites decreases expression of a host actin regulatory protein involved in C. rodentium and EHEC attachment to the gut epithelium via formation of actin pedestals. Our results reveal a noncanonical colonization resistance pathway against AE pathogens that features an unconventional role for DRD2 outside the nervous system in controlling actin cytoskeletal organization in the gut epithelium. Our findings may inspire prophylactic and therapeutic approaches targeting DRD2 with dietary or pharmacological interventions to improve gut health and treat gastrointestinal infections, which afflict millions globally.


Subject(s)
Citrobacter rodentium , Intestinal Mucosa , Receptors, Dopamine D2 , Tryptophan , Animals , Female , Humans , Male , Mice , Actin Cytoskeleton/drug effects , Actin Cytoskeleton/metabolism , Actins/metabolism , Bacterial Load/drug effects , Citrobacter rodentium/growth & development , Citrobacter rodentium/metabolism , Citrobacter rodentium/pathogenicity , Dietary Supplements , Disease Models, Animal , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/prevention & control , Escherichia coli Infections/microbiology , Escherichia coli Infections/prevention & control , Escherichia coli O157/pathogenicity , Escherichia coli O157/physiology , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Receptors, Dopamine D2/metabolism , Tryptophan/administration & dosage , Tryptophan/metabolism , Tryptophan/pharmacology
14.
Front Psychiatry ; 15: 1300739, 2024.
Article in English | MEDLINE | ID: mdl-38469030

ABSTRACT

Objective: The aim of this article was to review existing documents in the field of mobile-based EMA and EMI, provide an overview of current hot topics, and predict future development trends. Methods: We conducted a bibliometric study on mobile-based EMA and EMI publications that were collected from the Web of Science Core Collection database. Biblioshiny and CiteSpace were utilized to analyze scientific productions, leading sources, authors, affiliations, documents, research hot topics, keywords, and trend topics. Results: A total of 2222 documents related to EMA and EMI published between 1992 and 2023 were retrieved. In recent years, scholarly publications have generally increased in mobile-based EMA and EMI research, particularly in the last decade. JMIR mHealth and uHealth (n=86), as well as JMIR (n=73), showed the highest number of publications. The United States (n=1038), Germany (n=218) and Netherlands (n=175) were leading countries. Regarding keyword co-occurrence and trend topics analysis, mental health, health behaviors, and feasibility were hot topics in mobile-based EMA and EMI research. Future research trends included using EMA for tailoring EMI, just-in-time adaptive interventions (JITAI), and digital phenotyping. Conclusion: This bibliometric study on mobile-based EMA and EMI is a valuable resource for understanding the field's evolution and future trends. Our analysis indicates that EMA and EMI have great potential in health behaviors and mental health, but implementation should consider feasibility and reactivity issues carefully. Emerging trends include EMA-tailored EMI, JITAI, and digital phenotyping. In the future, strengthening multidisciplinary cooperation will be necessary to promote the continued development of the field.

15.
J Cancer Res Clin Oncol ; 150(3): 142, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38503944

ABSTRACT

PURPOSE: Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, and its precursors (carnitine, choline, betaine) have not been fully examined in relation to thyroid cancer (TC) risk. The aim of this study was to assess the value of TMAO and its precursors in diagnosis of benign and malignant thyroid nodules. METHODS: In this study, high-performance liquid chromatography-tandem mass spectrometry was utilized to measure the levels of plasma TMAO and its precursors (choline, carnitine, and betaine) in 215 TC patients, 63 benign thyroid nodules (BTN) patients and 148 healthy controls (HC). The distribution of levels of TMAO and its precursors among the three groups were compared by the Kruskal-Wallis test. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the sensitivity, specificity, and the predictive accuracy of single and combined biomarkers. RESULTS: In comparison to HC, TC showed higher levels of TMAO and lower levels of its precursors (carnitine, choline, and betaine) (all P < 0.001). Plasma choline (P < 0.01) and betaine (P < 0.05) were declined in BTN than HC. The levels of carnitine (P < 0.001) and choline (P < 0.05) were significantly higher in BTN than that in TC group. Plasma TMAO showed lower levels in TC with lymph node metastasis (101.5 (73.1-144.5) ng/ml) than those without lymph node metastasis (131 (84.8-201) ng/ml, P < 0.05). Combinations of these four metabolites achieved good performance in the differential diagnosis, with the area under the ROC curve of 0.703, 0.741, 0.793 when discriminating between TC and BTN, BTN and HC, TC and HC, respectively. CONCLUSION: Plasma TMAO, along with its precursors could serve as new biomarkers for the diagnosis of benign and malignant thyroid nodules.


Subject(s)
Betaine , Methylamines , Thyroid Nodule , Humans , Betaine/metabolism , Choline/metabolism , Carnitine/metabolism , Thyroid Nodule/diagnosis , Lymphatic Metastasis , Biomarkers
16.
IEEE Trans Pattern Anal Mach Intell ; 46(7): 4977-4992, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38300784

ABSTRACT

Transformers have been widely used for video processing owing to the multi-head self attention (MHSA) mechanism. However, the MHSA mechanism encounters an intrinsic difficulty for video inpainting, since the features associated with the corrupted regions are degraded and incur inaccurate self attention. This problem, termed query degradation, may be mitigated by first completing optical flows and then using the flows to guide the self attention, which was verified in our previous work - flow-guided transformer (FGT). We further exploit the flow guidance and propose FGT++ to pursue more effective and efficient video inpainting. First, we design a lightweight flow completion network by using local aggregation and edge loss. Second, to address the query degradation, we propose a flow guidance feature integration module, which uses the motion discrepancy to enhance the features, together with a flow-guided feature propagation module that warps the features according to the flows. Third, we decouple the transformer along the temporal and spatial dimensions, where flows are used to select the tokens through a temporally deformable MHSA mechanism, and global tokens are combined with the inner-window local tokens through a dual-perspective MHSA mechanism. FGT++ is experimentally evaluated to be outperforming the existing video inpainting networks qualitatively and quantitatively.

17.
Medicine (Baltimore) ; 103(4): e36074, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38277565

ABSTRACT

Intratumoral heterogeneity has been a hot topic of cancer research in recent years, which has become a part of resolving cancer metastasis, recurrence and drug resistance. Intratumoral heterogeneity shows that cells undergo different division and proliferation during the process of tumor development, and their genomic cells exist in the process of tumor development. Protein and epigenetic changes can lead to differences in proliferation, migration and invasion, sensitivity and pharmacological prognosis of tumor cells, promote sustainable development and development of cancer cells, produce greater adaptability, and lead to metastasis, recurrence and drug resistance of malignant tumors. In recent years, the molecular mechanism and clinical application of intratumoral heterogeneity have captivated widespread attention from researchers. In the era of precision medicine, oncologists attempt to improve the clinical efficacy of targeted tumor therapy via intratumoral heterogeneity. In this article, recent advances in the study of intratumoral heterogeneity, molecular mechanism of intratumoral heterogeneity, systematic evolution and quantification and clinical significance of tumor heterogeneity were reviewed.


Subject(s)
Clinical Relevance , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Prognosis
18.
JAMA Neurol ; 81(2): 118-125, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38190136

ABSTRACT

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown. Objective: To assess the efficacy of argatroban for END in AIS. Design, Setting, and Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study. Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy. Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78). Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END. Trial Registration: ClinicalTrials.gov Identifier: NCT04275180.


Subject(s)
Arginine/analogs & derivatives , Ischemic Stroke , Stroke , Sulfonamides , Adult , Humans , Male , Aged , Ischemic Stroke/drug therapy , Stroke/complications , Stroke/drug therapy , Pipecolic Acids/therapeutic use , Pipecolic Acids/adverse effects , Anticoagulants/therapeutic use
19.
J Stroke Cerebrovasc Dis ; 33(3): 107575, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38232582

ABSTRACT

AIM: This study aimed to evaluate the feasibility of transcranial color-coded sonography (TCCS) and contrast-enhanced ultrasound (CEUS) in assessing middle cerebral artery (MCA) stem stenosis or occlusion compared to digital subtraction angiography (DSA). METHODS: A total of 48 cases including 96 MCAs suspected stem stenosis or obstruction in the MCA were assessed by TCCS, CE-TCCS, and DSA. The diameters of the most severe stenosis (Ds), proximal normal artery (Dn), and diameter stenosis rate of MCA were measured using both the color doppler flow imaging (CDFI) modality of TCCS or CEUS and the CEUS imaging modality. The intraclass correlation coefficients (ICCs) and 95 % confidence intervals (CI) were evaluated, and a weighted Kappa value was used to evaluate the intra-observer agreement, inter-observer agreement, agreement between CDFI modality and DSA stenosis or occlusion, and agreement between CEUS imaging modality and DSA stenosis or occlusion. RESULTS: The ICC results indicated excellent repeatability and reproducibility (all ICCs > 0.75; weighted Kappa values >0.81). Compared with DSA, the weighted Kappa values and 95 % CIs of stenosis (the first measurement was taken by two observers) of CDFI modality and CEUS imaging modality were 0.175 (0.041, 0.308) and 0.779 (0.570, 0.988) for observers A and 0.181 (0.046, 0.316) and 0.779 (0.570, 0.988) for observers B respectively. CONCLUSION: This study indicates that inter- and intra-observer agreements were good for the direct method of measuring percentages of MCA stenosis by TCCS and CEUS. CEUS imaging modality is a new and reliable imaging modality approach to evaluate the MCAs stenosis and occlusion.


Subject(s)
Cerebrovascular Disorders , Middle Cerebral Artery , Humans , Middle Cerebral Artery/diagnostic imaging , Constriction, Pathologic , Angiography, Digital Subtraction/methods , Reproducibility of Results , Feasibility Studies , Ultrasonography, Doppler, Transcranial/methods , Sensitivity and Specificity
20.
Environ Toxicol ; 39(3): 1055-1071, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37694961

ABSTRACT

Cholesterol metabolism is crucial for cell survival and cancer progression. The prognostic patterns of genes linked to cholesterol metabolism (CMAGs) in CESC, however, have received very little attention in research. From public databases, TCGA-CESC cohorts with mRNA expression patterns and the accompanying clinical information of patients were gathered. Consensus clustering was used to find the molecular subtype connected to cholesterol metabolism. In the TCGA-CESC cohort, a predictive risk model with 28 CMAGs was created using Lasso-Cox regression. The function enrichment analysis between groups with high-and low-risk were investigated by employing GO, KEGG, and GSVA software. The immune cell infiltration was analyzed using ESTIMATE, CIBERSORT, and MCPCOUNTER methods. Finally, we select 7 genes in risk model for further multivariate Cox analysis, and ultimately a hub gene, CHIT1, was identified. Meanwhile, the function of CHIT1 was preliminarily verified in cell and mice tumor model. In conclusion, the abundance of the CHIT1 gene might be beneficial for forecasting the prognosis of CESC, demonstrating that cholesterol metabolism could be a promising treatment target for CESC.


Subject(s)
Uterine Cervical Neoplasms , Humans , Animals , Mice , Female , Lipid Metabolism , Cell Survival , Cholesterol
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