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1.
J Cell Mol Med ; 28(9): e18328, 2024 May.
Article En | MEDLINE | ID: mdl-38683130

Gallbladder cancer is a rare but fatal malignancy. However, the mechanisms underlying gallbladder carcinogenesis and its progression are poorly understood. The function of m6A modification and its regulators was still unclear for gallbladder cancer. The current study seeks to investigate the function of YTH m6A RNA-binding protein 1 (YTHDF1) in gallbladder cancer. Transcriptomic analysis and immunochemical staining of YTHDF1 in gallbladder cancer tissues revealed its upregulation compared to paracancerous tissues. Moreover, YTHDF1 promotes the proliferation assays, Transwell migration assays, and Transwell invasion assays of gallbladder cancer cells in vitro. And it also increased tumour growth in xenograft mouse model and metastases in tail vein injection model in vivo. In vitro, UHRF1 knockdown partly reversed the effects of YTHDF1 overexpression. Mechanistically, dual-luciferase assays proved that YTHDF1 promotes UHRF1 expression via direct binding to the mRNA 3'-UTR in a m6A-dependent manner. Overexpression of YTHDF1 enhanced UHRF1 mRNA stability, as demonstrated by mRNA stability assays, and Co-IP studies confirmed a direct interaction between YTHDF1 and PABPC1. Collectively, these findings provide new insights into the progression of gallbladder cancer as well as a novel post-transcriptional mechanism of YTHDF1 via stabilizing target mRNA.


Adenosine , Gallbladder Neoplasms , Gene Expression Regulation, Neoplastic , RNA-Binding Proteins , Ubiquitin-Protein Ligases , Animals , Female , Humans , Male , Mice , Adenosine/analogs & derivatives , CCAAT-Enhancer-Binding Proteins/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/metabolism , Mice, Nude , RNA Stability/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics
2.
Article En | MEDLINE | ID: mdl-38619440

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

3.
Opt Lett ; 49(6): 1612-1615, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38489464

We propose and demonstrate a novel, to the best of our knowledge, fiber-optic multipoint acoustic detection system based on a multiwavelength erbium-doped fiber (EDF) laser (MWEDFL) using the polarization-hole-burning effect with Fabry-Perot interferometers as the acoustic cavity-loss modulator. A polarization-wavelength-related filter is designed to assign a distinct polarization state to each laser wavelength. By adjusting the polarization state, the polarization-dependent loss and gain of each laser line are tuned to be equal, effectively suppressing the mode competition of EDF and enabling a stable MWEDFL. Each laser line serves as a separate channel for acoustic detection. Theoretical and experimental analyses are conducted to study the transient-response-amplification effect on the acoustic perturbation of the MWEDFL. The results show that the proposed MWEDFL exhibits an amplification effect on the sound-induced cavity-loss modulation, effectively enhancing the sensitivity by 13 dB compared to that obtained using an external-light-source demodulation method. In addition, the MWEDFL based on the PHB effect avoids cross talk between laser channels and can achieve high sensitivity and simultaneous multichannel acoustic detection.

4.
Sensors (Basel) ; 24(5)2024 Feb 25.
Article En | MEDLINE | ID: mdl-38475027

This study proposes a novel multipoint transducer system by utilizing the single-mode-multimode-thin-cladding fiber (SMTC) structure. This structure leverages the disparity in mode field diameter between the multimode fiber (MMF) and thin-cladding fiber (TCF) to generate high-amplitude ultrasonic signals safely and efficiently. The fabricated transducer exhibits signal amplitudes 2-3-fold higher compared to conventional laser-ultrasonic transducers. Simulation analysis investigates the impact of the length of the MMF and the diameter of the TCF on coupling efficiency. The coupling efficiency of individual transducer units can be accurately controlled by adjusting the length of the MMF. A three-point energy-balanced laser-ultrasonic transducer system was achieved, with improved energy conversion efficiencies, and the optimal thickness of candle soot nanoparticles (CSNPs) is experimentally determined. Additionally, we carried out experiments to compare the performance of the proposed SMTC-based transducer system under different material conditions using two different photoacoustic materials: graphite-epoxy resin and candle soot nanoparticle-polydimethylsiloxane (CSNP-PDMS) composite. CSNPs, as a cost-effective and easy-to-prepare composite material, exhibit higher photoacoustic conversion efficiency compared to graphite-epoxy resin. The proposed system demonstrates the potential for applications in non-destructive testing techniques.

5.
Cell Death Discov ; 10(1): 83, 2024 Feb 16.
Article En | MEDLINE | ID: mdl-38365891

Biliary tract cancers (BTCs) are relatively rare malignancies with a poor prognosis. For advanced BTCs, the efficacy of current chemotherapeutic approaches is limited. Consequently, there is an urgent need to deepen our understanding of the molecular mechanisms underlying BTC tumorigenesis and development for the exploration of effective targeted therapies. N6-methyladenosine (m6A), the most abundant RNA modifications in eukaryotes, is found usually dysregulated and involved in tumorigenesis, progression, and drug resistance in tumors. Numerous studies have confirmed that aberrant m6A regulators function as either oncogenes or tumor suppressors in BTCs by the reversible regulation of RNA metabolism, including splicing, export, degradation and translation. In this review, we summarized the current roles of the m6A regulators and their functional impacts on RNA fate in BTCs. The improved understanding of m6A modification in BTCs also provides a reasonable outlook for the exploration of new diagnostic strategies and efficient therapeutic targets.

6.
Abdom Radiol (NY) ; 49(1): 3-10, 2024 Jan.
Article En | MEDLINE | ID: mdl-37787963

OBJECTIVE: Our study aimed to determine whether radiomics models based on contrast-enhanced computed tomography (CECT) have considerable ability to predict serosal involvement in gallbladder cancer (GBC) patients. MATERIALS AND METHODS: A total of 152 patients diagnosed with GBC were retrospectively enrolled and divided into the serosal involvement group and no serosal involvement group according to paraffin pathology results. The regions of interest (ROIs) in the lesion on all CT images were drawn by two radiologists using ITK-SNAP software (version 3.8.0). A total of 412 features were extracted from the CT images of each patient. The Mann‒Whitney U test was applied to identify features with significant differences between groups. Seven machine learning algorithms and a deep learning model based on fully connected neural networks (f-CNNs) were used for radiomics model construction. The prediction efficacy of the models was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Through the Mann‒Whitney U test, 75 of the 412 features extracted from the CT images of patients were significantly different between groups (P < 0.05). Among all the algorithms, logistic regression achieved the highest performance with an area under the curve (AUC) of 0.944 (sensitivity 0.889, specificity 0.8); the f-CNN deep learning model had an AUC of 0.916, and the model showed high predictive power for serosal involvement, with a sensitivity of 0.733 and a specificity of 0.801. CONCLUSION: Radiomics models based on features derived from CECT showed convincing performances in predicting serosal involvement in GBC.


Deep Learning , Gallbladder Neoplasms , Humans , Gallbladder Neoplasms/diagnostic imaging , Radiomics , Retrospective Studies , Machine Learning
7.
Environ Sci Technol ; 57(51): 21535-21539, 2023 Dec 26.
Article En | MEDLINE | ID: mdl-38086081

Phosphorus (P) inputs to the biosphere have quadrupled in less than a century due to intensification of rock phosphate mining and the use of P fertilizers for crop production. Accumulation of P in soils can increase P transfers across the soil-water continuum that impair aquatic ecosystem function and water resource quality for society. However, what this accumulated P is called, and subsequent connotations of magnitude versus mechanism at pedon versus watershed scale, varies in the literature. We argue that the two commonly used terms of "residual" and "legacy" P, though often used interchangeably, hold distinct meanings and connotations. Tracing the historical origins and trajectories of these terms reveals that "residual P" refers to the magnitude of fertilizer P that remains in the soil after crop harvest, whereas "legacy P" refers to the mechanism of P transfer across the watershed and its long-term impacts on water quality. The use of "legacy P" in many cases refers to the residuality of anthropogenic P inputs, and thus should be "residual P". We recommend that the term "residual P" be used when referring to the accumulation of P in soils under agricultural management from past inputs, and the term "legacy P" be used when referring to the transfer of P within watersheds. The intentional and thus consistent use of residual versus legacy P stands to provide important nuance in the environmental sciences and overlapping fields of agronomy and biogeochemistry.


Ecosystem , Phosphorus , Phosphorus/analysis , Agriculture , Soil , Water Quality , Fertilizers/analysis
8.
Future Med Chem ; 15(20): 1823-1841, 2023 10.
Article En | MEDLINE | ID: mdl-37902028

Aim: Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Results: These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound A1 possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC50 = 0.054 ± 0.004 µM; MAO-B: IC50 = 3.25 ± 0.20 µM), moderate inhibitory effects on self-mediated amyloid-ß (Aß) aggregation and antioxidant activity. In addition, compound A1 exhibited low neurotoxicity. More importantly, compound A1 showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. Conclusion: All results suggest that compound A1 may become a promising lead of anti-AD drug for further development.


Acetylcholinesterase , Alzheimer Disease , Animals , Mice , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amyloid beta-Peptides , Cholinesterase Inhibitors/pharmacology , Drug Design , Indans/pharmacology , Monoamine Oxidase/metabolism , Monoamine Oxidase Inhibitors , Structure-Activity Relationship
9.
J Environ Qual ; 52(6): 1063-1079, 2023.
Article En | MEDLINE | ID: mdl-37725393

To monitor and meet water quality objectives, it is necessary to understand and quantify the contribution of nonpoint sources to total phosphorus (P) loading to surface waters. However, the contribution of streambank erosion to surface water P loads remains unclear and is typically unaccounted for in many nutrient loading assessments and policies. As a result, agricultural contributions of P are overestimated, and a potentially manageable nonpoint source of P is missed in strategies to reduce loads. In this perspective, we review and synthesize the results of a special symposium at the 2022 ASA-CSSA-SSSA annual meeting in Baltimore, MD, that focused on streambank erosion and its contributions to P loading of surface waters. Based on discussions among researchers and policy experts, we overview the knowns and unknowns, propose next steps to understand streambank erosion contribution to P export budgets, and discuss implications of the science of streambank erosion for policy and nutrient loss reduction strategies.


Environmental Monitoring , Phosphorus , Environmental Monitoring/methods , Phosphorus/analysis , Water Quality , Agriculture , Nutrients
10.
Cancer Sci ; 114(11): 4299-4313, 2023 Nov.
Article En | MEDLINE | ID: mdl-37700438

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNA and involved in the carcinogenesis of various malignancies. However, the functions and mechanisms of m6A in gallbladder cancer (GBC) remain unclear. In this study, we investigated the role and underlying mechanism of the RNA-binding protein YT521-B homology domain-containing family protein 2 (YTHDF2), an m6A reader, in GBC. Herein, we detected that YTHDF2 was remarkably upregulated in GBC tissues compared to normal gallbladder tissues. Functionally, YTHDF2 overexpression promoted the proliferation, tumor growth, migration, and invasion of GBC cells while inhibiting the apoptosis in vitro and in vivo. Conversely, YTHDF2 knockdown induced opposite results. Mechanistically, we further investigated the underlying mechanism by integrating RNA immunoprecipitation sequencing (RIP-seq), m6A-modified RIP-seq, and RNA sequencing, which revealed that death-associated protein kinase 3 (DAPK3) is a direct target of YTHDF2. YTHDF2 binds to the 3'-UTR of DAPK3 mRNA and facilitates its degradation in an m6A-dependent manner. DAPK3 inhibition restores the tumor-suppressive phenotype induced by YTHDF2 deficiency. Moreover, the YTHDF2/DAPK3 axis induces the resistance of GBC cells to gemcitabine. In conclusion, we reveal the oncogenic role of YTHDF2 in GBC, demonstrating that YTHDF2 increases the mRNA degradation of the tumor suppressor DAPK3 in an m6A-dependent way, which promotes GBC progression and desensitizes GBC cells to gemcitabine. Our findings provide novel insights into potential therapeutic strategies for GBC.


Gallbladder Neoplasms , Gemcitabine , Humans , Gallbladder Neoplasms/drug therapy , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Transcription Factors/metabolism , RNA , Death-Associated Protein Kinases/metabolism
11.
ACS Appl Mater Interfaces ; 15(36): 42354-42368, 2023 Sep 13.
Article En | MEDLINE | ID: mdl-37642201

Covalent organic frameworks (COFs) have revealed enormous application prospects for cancer therapeutics recently, but their assembly systems face considerable challenges, such as the codelivery of hydrophobic and hydrophilic protein drugs with different physicochemical properties for in vivo delivery and release, as well as endosomal/lysosomal escape of protein drugs. To address these issues, we leveraged the high specific surface area, lipotropism, and structural tunability of boronate ester-linked COFs (COF-1) for the construction of advanced drug delivery systems. We first encapsulated the small-molecule drug doxorubicin (DOX) into a lipophilic COF (COF-1@DOX) and immobilized the functional protein drug ribonuclease A (RNase A) on the surface of the COF (RNase A-COF-1@DOX). We then created a novel composite delivery system (RNase A-COF-1@DOX gel) by cross-linking an albumin-oxygenated hydrogel (gel) network into the pores of COFs, allowing targeted codelivery of protein and small-molecule drugs in vivo. Using in-living body and multichannel fluorescence imaging, we analyzed the in vivo codelivery of protein and small-molecule drugs in a Lewis lung carcinoma (LLC) model. Finally, we applied the RNase A-COF-1@DOX gel to treat lung cancer in mice. This study paves an avenue for constructing COF-based drug delivery systems for lung cancer treatment and holds the potential to be extended to other types of cancer for more effective and targeted therapeutic treatments.


Lung Neoplasms , Metal-Organic Frameworks , Animals , Mice , Hydrogels/pharmacology , Ribonuclease, Pancreatic , Lung Neoplasms/drug therapy , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Ribonucleases , Metal-Organic Frameworks/pharmacology
12.
PLoS One ; 18(8): e0285401, 2023.
Article En | MEDLINE | ID: mdl-37552694

Alpinia oxyphylla Fructus, called Yizhi in Chinese, is the dried fruit of Alpinia oxyphylla Miquel. It has been used in traditional Chinese medicine to treat dementia and memory defects of Alzheimer's disease for many years. However, the underlying mechanism is still unclear. In this study, we used a rat Alzheimer's disease model on intrahippocampal injection of aggregated Aß1-42 to study the effects of Alpinia oxyphylla Fructus. A brain and plasma dual-channel metabolomics approach combined with multivariate statistical analysis was further performed to determine the effects of Alpinia oxyphylla Fructus on Alzheimer's disease animals. As a result, in the Morris water maze test, Alpinia oxyphylla Fructus had a clear ability to ameliorate the impaired learning and memory of Alzheimer's disease rats. 11 differential biomarkers were detected in AD rats' brains. The compounds mainly included amino acids and phospholipids; after Alpinia oxyphylla Fructus administration, 9 regulated biomarkers were detected compared with the AD model group. In the plasma of AD rats, 29 differential biomarkers, primarily amino acids, phospholipids and fatty acids, were identified; After administration, 23 regulated biomarkers were detected. The metabolic pathways of regulated metabolites suggest that Alpinia oxyphylla Fructus ameliorates memory and learning deficits in AD rats principally by regulating amino acid metabolism, lipids metabolism, and energy metabolism. In conclusion, our results confirm and enhance our current understanding of the therapeutic effects of Alpinia oxyphylla Fructus on Alzheimer's disease. Meanwhile, our work provides new insight into the potential intervention mechanism of Alpinia oxyphylla Fructus for Alzheimer's disease treatment.


Alpinia , Alzheimer Disease , Rats , Animals , Alzheimer Disease/metabolism , Brain/metabolism , Maze Learning , Metabolomics , Plant Extracts/pharmacology , Plant Extracts/therapeutic use
13.
iScience ; 26(8): 107348, 2023 Aug 18.
Article En | MEDLINE | ID: mdl-37554442

Covalent organic frameworks (COFs) have garnered enormous attention in anti-cancer therapy recently. However, the intrinsic drawbacks such as poor biocompatibility and low target-specificity greatly restrain the full clinical implementation of COF. Herein, we report a biomimetic multifunctional COF nanozyme, which consists of AIEgen-based COF (TPE-s COF) with encapsulated gold nanoparticles (Au NPs). The nanozyme was co-cultured with HepG2 cells until the cell membrane was fused with lipophilic TPE-s COF-Au@Cisplatin. By using the cryo-shocking method, we fabricated an inactivated form of the TPE-s COF-Au@Cisplatin nanozyme endocytosed in the HepG2 cell membrane (M@TPE-s COF-Au@Cisplatin), which lost their proliferative ability and pathogenicity. Upon laser irradiation, the M@TPE-s COF-Au@Cisplatin nanozymes cleaved, thereby releasing the TPE-s COF-Au nanozyme and Cisplatin to exert their photothermal and drug therapeutic effect. This work opens a new avenue to the synthesis of tumor-derived fluorescent TPE-s COF-Au nanozymes for highly efficient, synergetic, and targeted chemo-photothermal combination therapy of liver cancer.

14.
Int J Med Sci ; 20(5): 595-605, 2023.
Article En | MEDLINE | ID: mdl-37082732

Background: Aim to investigate bile acid profile changes and the Farnesoid X receptor (FXR) status after ileotransposition (IT), and reveal its possible hypoglycemic mechanism. Methods: Twenty male diabetic rats were randomly assigned into the IT group and the sham IT (SH) group. Bile acid profiles were measured using an ultra-performance liquid chromatography-tandem mass spectrometry. Glucose metabolism was monitored after oral administration of FXR inhibitor and agonist. And the expression of key FXR target genes were measured. Results: The levels of ß-muricholic acid (P = 0.047), tauro-α-muricholic acid and tauro-ß-muricholic acid (P < 0.001) in plasma in the IT group were higher than those in the SH group, and the levels of taurocholic acid (P = 0.049) and turoursodeoxycholic acid (P = 0.030) were lower than those in the SH group. After inhibition of intestinal FXR, the glucose metabolism in the SH group was improved. When FXR agonist was given, the blood glucose level was increased in both groups. After sacrifice, the levels of glycoursodeoxycholic acid, tauro-α-muricholic acid and tauro-ß-muricholic acid in liver and ileum tissues were higher than those in the SH group (P < 0.05), the level of α- muricholic acid (P < 0.001) in liver tissues were lower than that in the SH group. Moreover, the expression of CYP7A1 mRNA (P < 0.001) and FGF15 mRNA (P = 0.001) in the IT group was significantly higher, and the expression of PEPCK mRNA (P = 0.004), SREPB1c mRNA (P = 0.005) and SRB1 mRNA (P = 0.001) were significantly lower than that in the SH group. Conclusions: We demonstrate a remarkable heterogeneity of BA profiles after IT, FXR activation might has a detrimental effect on glucose metabolism.


Diabetes Mellitus, Experimental , Hypoglycemic Agents , Rats , Male , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/metabolism , Ileum , Bile Acids and Salts , Liver , Glucose/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism
15.
Front Pharmacol ; 14: 1090895, 2023.
Article En | MEDLINE | ID: mdl-36992841

Background: Ferroptosis is an iron-dependent programmed cell death process, and studies have confirmed that it plays an important regulatory role in the occurrence and development of various malignancies including hepatocellular carcinoma (HCC). In addition, the role of abnormally expressed long non-coding RNAs (lncRNAs) in regulating and driving the occurrence and development of HCC has attracted more and more attention. However, there is still a lack of research on the role of ferroptosis-related lncRNAs in the prognosis prediction of HCC patients. Method: In this study, we used the Pearson test method to analyze the association between differentially expressed lncRNAs and ferroptosis-related genes in HCC and normal tissues obtained from The Cancer Genome Atlas (TCGA), and found 68 aberrantly expressed and prognosis-related ferroptosis-related lncRNAs. Based on this, we established an HCC prognostic model composed of 12 ferroptosis-related lncRNAs. In addition, HCC patients were divided into a high-risk group and a low-risk group according to the risk score of this 12 ferroptosis-related lncRNAs prognostic model. Gene enrichment analysis indicated that ferroptosis-related lncRNA-based expression signatures may regulate HCC immune microenvironment signaling pathways through ferroptosis, chemical carcinogenesis-reactive oxygen species, and NK cell-mediated cytotoxicity pathways. In addition, immune cell correlation analysis showed that there were significant differences in immune infiltrating cell subtypes, such as Th cells, macrophages, monocytes, and Treg cells between the two groups. In addition, the expression of multiple immune checkpoint molecules was found to be significantly increased in the high-risk group (eg, PD1, CTLA-4, CD86, etc.). Results: Our research provides a new method for predicting prognosis using a ferroptosis-related lncRNA expression signature prognostic model in hepatocellular carcinoma. And it provides new tools for predicting patient response and adverse effects of immunotherapy. Conclusion: In conclusion, ferroptosis-related lncRNA expression signatures can be used to construct a prognostic prediction model to predict the overall survival of HCC patients, and can be used as an independent influencing factor for prognosis. Further analysis showed that ferroptosis-related lncRNAs may affect the efficacy of immunotherapy in patients with HCC by altering the tumor microenvironment, so this model may serve as a new indicator of the response and irAEs of HCC to immunotherapy.

16.
J Med Chem ; 66(7): 5118-5153, 2023 04 13.
Article En | MEDLINE | ID: mdl-36997840

High oxidative phosphorylation (OXPHOS) happens in some tumors, which depends on OXPHOS for energy supply, particularly in slow-cycling tumor cells. Therefore, targeting human mitochondrial RNA polymerase (POLRMT) to inhibit mitochondrial gene expression emerges as a potential therapeutic strategy to eradicate tumor cells. In this work, exploration and optimization of the first-in-class POLRMT inhibitor IMT1B and its SAR led to the identification of a novel compound D26, which exerted a strong antiproliferative effect on several cancer cells and decreased mitochondrial-related genes expression. In addition, mechanism studies demonstrated that D26 arrested cell cycle at the G1 phase and had no effect on apoptosis, depolarized mitochondria, or reactive oxidative stress generation in A2780 cells. Importantly, D26 exhibited more potent anticancer activity than the lead IMT1B in A2780 xenograft nude mice and had no observable toxic effect. All results suggest that D26 deserves to be further investigated as a potent and safe antitumor candidate.


Antineoplastic Agents , Ovarian Neoplasms , Animals , Mice , Humans , Female , Cell Line, Tumor , RNA, Mitochondrial/metabolism , Mice, Nude , Xenograft Model Antitumor Assays , Ovarian Neoplasms/drug therapy , DNA-Directed RNA Polymerases/metabolism , Mitochondria , Apoptosis , Cell Proliferation , Antineoplastic Agents/therapeutic use
17.
PLoS One ; 18(2): e0267633, 2023.
Article En | MEDLINE | ID: mdl-36757967

The poor and rich optimization algorithm (PRO) is a new bio-inspired meta-heuristic algorithm based on the behavior of the poor and the rich. PRO suffers from low convergence speed and premature convergence, and easily traps in the local optimum, when solving very complex function optimization problems. To overcome these limitations, this study proposes an improved poor and rich optimization (IPRO) algorithm. First, to meet the requirements of convergence speed and swarm diversity requirements across different evolutionary stages of the algorithm, the population is dynamically divided into the poor and rich sub-population. Second, for the rich sub-population, this study designs a novel individual updating mechanism that learns from the evolution information of the global optimum individual and that of the poor sub-population simultaneously, to further accelerate convergence speed and minimize swarm diversity loss. Third, for the poor sub-population, this study designs a novel individual updating mechanism that improves some evolution information by learning alternately from the rich and Gauss distribution, gradually improves evolutionary genes, and maintains swarm diversity. The IPRO is then compared with four state-of-the-art swarm evolutionary algorithms with various characteristics on the CEC 2013 test suite. Experimental results demonstrate the competitive advantages of IPRO in convergence precision and speed when solving function optimization problems.


Algorithms , Problem Solving , Computer Simulation , Learning , Heuristics
18.
Int J Anal Chem ; 2023: 3754549, 2023.
Article En | MEDLINE | ID: mdl-36820244

Scutellariabaicalensis Georgi, an important perennial herb, is widely distributed and used all over the world. The root of S. baicalensis (Radix Scutellaria) is rich in flavonoids with a variety of bioactive effects and is widely used in clinic. The different geographical and climatic conditions of different cultivated areas of S. baicalensis lead to the differences of the main components in Radix Scutellaria. The main objective of this study was to evaluate the difference of flavonoid content in Radix Scutellaria from different cultivated areas in China. The mobile phase system, elution gradient, detection wavelength, and other chromatographic conditions for high-performance liquid chromatography-diode array detection (HPLC-DAD) determination of 8 flavonoids in Radix Scutellaria were optimized. The contents of flavonoids in 38 samples of Radix Scutellaria collected from seven main genuine cultivated areas were determined, and the correlation between the content, cultivated area, and the biological activities of Radix Scutellaria was compared. The results implied that baicalin, wogonoside, and baicalein were the three main flavonoids with the highest contents in Radix Scutellaria. The content of flavonoids in different cultivated areas was very different, which had significant regionality and was closely related to the natural conditions of various places. The antioxidant and antitumor activities of the extract of Radix Scutellaria were closely related to the content of flavonoids, and high contents of baicalin, wogonoside, and baicalein positively improved biological activities.

19.
Sci Total Environ ; 857(Pt 1): 159038, 2023 Jan 20.
Article En | MEDLINE | ID: mdl-36174684

Quantifying spatiotemporal dynamics of soil organic carbon (SOC) stocks is needed to understand the impact of land use change and can help target carbon sequestration efforts. In the recently and radically transformed landscapes of the state of Illinois, U.S.A., we evaluated surface SOC stocks under land use change using a space-for-time substitution method over 167 years. Additionally, we determined SOC stocks for the A horizon vs 0-30 cm depth to evaluate pedogenically-informed vs more commonly used fixed depth approaches. Legacy soil datasets from 1980 to 2012 were combined with environmental covariates using a random forest algorithm. To more accurately estimate pre-agricultural land use SOC stocks (i.e., pre-1845), SOC observations collected from soils under native prairie and forest were extracted from peer-reviewed publications. The model was validated on 25 % of the total 627 test data (RA-hor2: 0.59 and R0-302: 0.56; RMSEA-hor: 20.5 and RMSE0-30:19.3 Mg/ha) independent of the 75 % of data for calibration (R2: 0.91; RMSEA-hor:10.1 and RMSE0-30:9.6 Mg/ha). SOC stocks were largest under prairie (A horizon: 156.1 Mg/ha; 0-30 cm: 152.4 Mg/ha) and lowest under pasture (A horizon: 33.2, 0-30 cm: 44.6 Mg/ha). SOC stocks varied less by soil order than by land use. Between 1845 and 2012, surface SOC stocks decreased for most of Illinois, with greatest losses in central (-16.3 Mg/ha) and east-central Illinois (-47.0 Mg/ha) where approximately 80 % of prairie was converted to cropland. A slight increase in surface SOC stocks occurred in the unglaciated northwest region and the less recently glaciated south region, as well as in alluvial corridors. This study (i) highlights how estimating spatiotemporal dynamics of surface SOC stocks over centennial timescales can benefit from including measures of SOC under native land use not usually contained in legacy pedon datasets, and (ii) illustrates the potential of identifying localized hotspots of historical SOC loss and thus deficits that can be prioritized for carbon sequestration efforts.


Carbon , Soil , Carbon/analysis , Grassland , Carbon Sequestration , Illinois
20.
Rev. bras. med. esporte ; 29: e2022_0324, 2023. tab
Article En | LILACS-Express | LILACS | ID: biblio-1423297

ABSTRACT Introduction Suspension training develops the physical fitness of a swimmer and improves his or her abilities. The specific fitness of a swimmer is the body's ability to adapt to load in swimming. This is also a comprehensive reflection of their physical function, conditioning, athletic ability, and overall health. Objective This study aimed to analyze the effect of suspension training on swimmers' balance, abdominal center strength, and athletic performance. Methods This paper selects several swimmers as research volunteers. They were randomly divided into experimental and control groups. Both of them underwent physical training for three months. The experimental group adopted the suspension training method. The control group used traditional training methods. Mathematical statistics performed data analysis in both groups. Results The physical fitness of the two groups of swimmers was improved substantially after the experiment (P<0.05). The strength balance ability of the experimental group showed better performance(P<0.05). There was a significant difference between the experimental and control groups in the results of fitness index tests (P<0.01). Conclusion Suspension training has a prominent effect on the physical development of swimmers. This modality proved a better efficacy on swimmers' performance. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.


RESUMO Introdução O treinamento em suspensão desenvolve a aptidão física de um nadador e aprimora suas habilidades. A aptidão física específica de um nadador é a capacidade corporal de adaptação à carga na natação. Isto é também um reflexo abrangente de sua função física, condicionamento, habilidade atlética e saúde geral. Objetivo Este estudo teve como objetivo analisar o efeito do treinamento em suspensão no equilíbrio da força do centro abdominal e no desempenho atlético dos nadadores. Métodos Este artigo seleciona vários nadadores como voluntários de pesquisa. Eles foram divididos aleatoriamente em grupo experimental e grupo de controle. Ambos foram submetidos a treinamento físico durante três meses. O grupo experimental adotou o método de treinamento em suspensão. O grupo de controle utilizou métodos de treinamento tradicionais. A análise dos dados nos dois grupos foi executada por estatísticas matemáticas. Resultados A aptidão física dos dois grupos de nadadores foi aprimorada substancialmente após o experimento (P<0,05). A capacidade de equilíbrio de força do grupo experimental demonstrou um melhor desempenho(P<0,05). Houve uma diferença significativa entre os grupos experimental e de controle nos resultados dos testes de índice de aptidão física (P<0,01). Conclusão O treinamento de suspensão tem um efeito destacado sobre o desenvolvimento físico dos nadadores. Esta modalidade comprovou uma melhor eficácia sobre o desempenho dos nadadores.Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción El entrenamiento en suspensión desarrolla la aptitud física de un nadador y mejora sus habilidades. La condición física específica de un nadador es la capacidad del cuerpo para adaptarse a la carga en la natación. También es un reflejo exhaustivo de su función física, su acondicionamiento, su capacidad atlética y su salud en general. Objetivo Este estudio tiene como objetivo analizar el efecto del entrenamiento en suspensión sobre el equilibrio de la fuerza del centro abdominal y el rendimiento deportivo de los nadadores. Métodos Este trabajo selecciona a varios nadadores como voluntarios para la investigación. Se dividieron aleatoriamente en grupo experimental y grupo de control. Ambos fueron sometidos a un entrenamiento físico durante tres meses. El grupo experimental adoptó el método de entrenamiento en suspensión. El grupo de control utilizó métodos de entrenamiento tradicionales. El análisis de los datos en ambos grupos se realizó mediante estadística matemática. Resultados La aptitud física de los dos grupos de nadadores mejoró sustancialmente después del experimento (P<0,05). La capacidad de equilibrio de la fuerza del grupo experimental mostró un mejor rendimiento (P<0,05). Hubo una diferencia significativa entre los grupos experimental y de control en los resultados de las pruebas del índice de aptitud física (P<0,01). Conclusión El entrenamiento en suspensión tiene un efecto destacado en el desarrollo físico de los nadadores. Esta modalidad demostró una mayor eficacia en el rendimiento de los nadadores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

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