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1.
Adv Healthc Mater ; : e2401567, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38962848

ABSTRACT

Copper is indispensable to organisms, while its homeostatic imbalance may interference normal cellular physiological processes and even induce cell death. Artificially regulating cellular copper content provides a viable strategy to activate antineoplastic effect. In light of this, a copper ions homeostasis perturbator (CuP-CL) with cinnamaldehyde (Cin) packaging and thermosensitive liposome coating is reported. Following laser exposure, the doping of Cu2+ in polydopamine initiates enhanced photothermal therapy (PTT) and unlocks the outer layer of liposome, leading to the release of copper ions and Cin in tumor microenvironment with mild acidity and high glutathione (GSH) levels. The liberative Cu2+ can evoke cuproptosis and chemodynamic therapy (CDT). Meanwhile, leveraging the merits of H2O2 supply and GSH consumption, Cin serves as a tumor microenvironment regulator to amplify Cu2+ mediated cuproptosis and CDT. Additionally, the positive feedback effects of "laser-triggered PTT, PTT accelerates reactive oxygen species (ROS) generation, ROS amplifies lipid peroxide (LPO) accumulation, LPO mediates heat shock proteins (HSPs) clearance, down-regulated HSPs promote PTT" entailed the overall benefit to therapeutic outcomes. Both in vitro and in vivo results corroborate the remarkable antineoplastic performance of CuP-CL by the synergy of cuproptosis/CDT/PTT. Collectively, based on the three-pronged approach, this work plots a viable multimodal regimen for cancer therapy.

2.
Heliyon ; 10(12): e32570, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38975140

ABSTRACT

Prediction of student academic performance is still a problem because of the limitations of the existing methods specifically low generalizability and lack of interpretability. This study suggests a new approach that deals with the current problems and provides more reliable predictions. The proposed approach combines the information gain (IG) and Laplacian score (LS) for feature selection. In this feature selection scheme, combination of IG and LS is used for ranking features and then, Sequential Forward Selection mechanism is used for determining the most relevant indicators. Also, combination of random forest algorithm with a genetic algorithm for is introduced for multi-class classification. This approach strives to attain more accuracy and reliability than current techniques. The case study shows the proposed strategy can predict performance of students with average accuracy of 93.11 % which shows a minimum improvement of 2.25 % compared to the baseline methods. The findings were further confirmed by the analysis of different evaluation metrics (Accuracy, Precision, Recall, F-Measure) to prove the efficiency of the proposed mechanism.

3.
World J Gastroenterol ; 30(14): 1990-2005, 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38681129

ABSTRACT

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive tract, and endoscopic submucosal dissection (ESD) is the preferred treatment for early-stage gastric cancer. The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD. AIM: To analyze the features of gastric mucosal tumors at different differentiation levels, and to explore the prognostic factors of ESD. METHODS: We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021, according to the latest Japanese guidelines (sixth edition), and divided them into low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and differentiated and undifferentiated early carcinoma. They are followed up by endoscopy, chest and abdominal computed tomography at 3, 6 and 12 months after ESD. We compared clinicopathologic characteristics, ESD efficacy, and complications with different degrees of differentiation, and analyzed the related factors associated with ESD. RESULTS: HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients (P < 0.001) and accounted for more 0-IIc (P < 0.001), atrophic gastritis was common (P < 0.001), and irregular microvascular patterns (IMVPs) and demarcation lines (DLs) were more obvious (P < 0.001). There was more infiltration in the undifferentiated carcinoma tissue (P < 0.001), more abnormal folds and poorer mucosal peristalsis (P < 0.001), and more obvious IMVPs, irregular microsurface patterns and DLs (P < 0.05) than in the LGIN and HGIN tissues. The disease-free survival rates at 2, 5, and 8 years after ESD were 95.0%, 90.1%, and 86.9%, respectively. Undifferentiated lesions (HR 5.066), white moss (HR 7.187), incomplete resection (HR 3.658), and multiple primary cancers (HR 2.462) were significantly associated with poor prognosis. CONCLUSION: Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics, which are closely related to the safety and efficacy of ESD.


Subject(s)
Endoscopic Mucosal Resection , Gastric Mucosa , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Endoscopic Mucosal Resection/adverse effects , Endoscopic Mucosal Resection/methods , Male , Female , Middle Aged , Retrospective Studies , Gastric Mucosa/surgery , Gastric Mucosa/pathology , Gastric Mucosa/diagnostic imaging , Aged , Treatment Outcome , Prognosis , Adult , Carcinoma in Situ/surgery , Carcinoma in Situ/pathology , Cell Differentiation , Neoplasm Grading , Gastroscopy/adverse effects , Gastroscopy/methods , Time Factors , Neoplasm Staging , Follow-Up Studies
4.
Biomaterials ; 309: 122574, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38670032

ABSTRACT

As an iron dependent regulatory cell death process driven by excessive lipid peroxides (LPO), ferroptosis is recognized as a powerful weapon for pancreatic cancer (PC) therapy. However, the tumor microenvironment (TME) with hypoxia and elevated glutathione (GSH) expression not only inhibits LPO production, but also induces glutathione peroxidase 4 (GPX4) mediated LPO clearance, which greatly compromise the therapeutic outcomes of ferroptosis. To address these issues, herein, a novel triple-enhanced ferroptosis amplifier (denoted as Zal@HM-PTBC) is rationally designed. After intravenous injection, the overexpressed H2O2/GSH in TME induces the collapse of Zal@HM-PTBC and triggers the production of oxygen and reactive oxygen species (ROS), which synergistically amplify the degree of lipid peroxidation (broaden sources). Concurrently, GSH consumption because of the degradation of the hollow manganese dioxide (HM) significantly weakens the activity of GPX4, resulting in a decrease in LPO clearance (reduce expenditure). Moreover, the loading and site-directed release of zalcitabine further promotes autophagy-dependent LPO accumulation (enhance effectiveness). Both in vitro and in vivo results validated that the ferroptosis amplifier demonstrated superior specificity and favorable therapeutic responses. Overall, this triple-enhanced LPO accumulation strategy demonstrates the ability to facilitate the efficacy of ferroptosis, injecting vigorous vitality into the treatment of PC.


Subject(s)
Ferroptosis , Glutathione , Lipid Peroxides , Pancreatic Neoplasms , Ferroptosis/drug effects , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Animals , Lipid Peroxides/metabolism , Humans , Cell Line, Tumor , Glutathione/metabolism , Mice , Manganese Compounds/chemistry , Oxides/chemistry , Reactive Oxygen Species/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Tumor Microenvironment/drug effects , Mice, Nude , Hydrogen Peroxide/metabolism , Lipid Peroxidation/drug effects , Mice, Inbred BALB C
5.
Eur Radiol ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627290

ABSTRACT

OBJECTIVES: To build self-supervised foundation models for multicontrast MRI of the whole brain and evaluate their efficacy in assisting diagnosis of brain tumors. METHODS: In this retrospective study, foundation models were developed using 57,621 enhanced head MRI scans through self-supervised learning with a pretext task of cross-contrast context restoration with two different content dropout schemes. Downstream classifiers were constructed based on the pretrained foundation models and fine-tuned for brain tumor detection, discrimination, and molecular status prediction. Metrics including accuracy, sensitivity, specificity, and area under the ROC curve (AUC) were used to evaluate the performance. Convolutional neural networks trained exclusively on downstream task data were employed for comparative analysis. RESULTS: The pretrained foundation models demonstrated their ability to extract effective representations from multicontrast whole-brain volumes. The best classifiers, endowed with pretrained weights, showed remarkable performance with accuracies of 94.9, 92.3, and 80.4%, and corresponding AUC values of 0.981, 0.972, and 0.852 on independent test datasets in brain tumor detection, discrimination, and molecular status prediction, respectively. The classifiers with pretrained weights outperformed the convolutional classifiers trained from scratch by approximately 10% in terms of accuracy and AUC across all tasks. The saliency regions in the correctly predicted cases are mainly clustered around the tumors. Classifiers derived from the two dropout schemes differed significantly only in the detection of brain tumors. CONCLUSIONS: Foundation models obtained from self-supervised learning have demonstrated encouraging potential for scalability and interpretability in downstream brain tumor-related tasks and hold promise for extension to neurological diseases with diffusely distributed lesions. CLINICAL RELEVANCE STATEMENT: The application of our proposed method to the prediction of key molecular status in gliomas is expected to improve treatment planning and patient outcomes. Additionally, the foundation model we developed could serve as a cornerstone for advancing AI applications in the diagnosis of brain-related diseases.

6.
Article in English | MEDLINE | ID: mdl-38573002

ABSTRACT

Aims: Erythropoiesis is controlled by several factors, including oxygen level under different circumstances. However, the role of hypoxia in erythroid differentiation and the underlying mechanisms are poorly understood. We studied the effect and mechanism of hypoxia on erythroid differentiation of K562 cells and observed the effect of hypoxia on early erythropoiesis of zebrafish. Results: Compared with normal oxygen culture, both hemin-induced erythroid differentiation of K562 cells and the early erythropoiesis of zebrafish were inhibited under hypoxic treatment conditions. Hypoxia-inducible factor 1 alpha (HIF1α) plays a major role in the response to hypoxia. Here, we obtained a stable HIF1α knockout K562 cell line using the CRISPR-Cas9 technology and further demonstrated that HIF1α knockout promoted hemin-induced erythroid differentiation of K562 cells under hypoxia. We demonstrated an HIF1-mediated induction of the nuclear factor interleukin-3 (NFIL3) regulated in K562 cells under hypoxia. Interestingly, a gradual decrease in NFIL3 expression was detected during erythroid differentiation of erythropoietin-induced CD34+ hematopoietic stem/progenitor cells (HSPCs) and hemin-induced K562 cells. Notably, erythroid differentiation was inhibited by enforced expression of NFIL3 under normoxia and was promoted by the knockdown of NFIL3 under hypoxia in hemin-treated K562 cells. In addition, a target of NFIL3, pim-1 proto-oncogene, serine/threonine kinase (PIM1), was obtained by RNA microarray after NFIL3 knockdown. PIM1 can rescue the inhibitory effect of NFIL3 on hemin-induced erythroid differentiation of K562 cells. Innovation and Conclusion: Our findings demonstrate that the HIF1α-NFIL3-PIM1 signaling axis plays an important role in erythroid differentiation under hypoxia. These results will provide useful clues for preventing the damage of acute hypoxia to erythropoiesis.

7.
Exp Cell Res ; 437(1): 113994, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38479704

ABSTRACT

m6A modification has been studied in tumors, but its role in host anti-tumor immune response and TAMs polarization remains unclear. The fatty acid oxidation (FAO) process of TAMs is also attracting attention. A co-culture model of colorectal cancer (CRC) cells and macrophages was used to simulate the tumor microenvironment. Expression changes of m6A demethylase genes FTO and ALKBH5 were screened. ALKBH5 was further investigated. Gain-of-function experiments were conducted to study ALKBH5's effects on macrophage M2 polarization, CRC cell viability, proliferation, migration, and more. Me-RIP and Actinomycin D assays were performed to study ALKBH5's influence on CPT1A, the FAO rate-limiting enzyme. AMP, ADP, and ATP content detection, OCR measurement, and ECAR measurement were used to explore ALKBH5's impact on macrophage FAO level. Rescue experiments validated ALKBH5's mechanistic role in macrophage M2 polarization and CRC malignant development. In co-culture, CRC cells enhance macrophage FAO and suppress m6A modification in M2 macrophages. ALKBH5 was selected as the gene for further investigation. ALKBH5 mediates CPT1A upregulation by removing m6A modification, promoting M2 macrophage polarization and facilitating CRC development. These findings indicate that ALKBH5 enhances fatty acid metabolism and M2 polarization of macrophages by upregulating CPT1A, thereby promoting CRC development.


Subject(s)
Colorectal Neoplasms , Macrophages , Humans , Up-Regulation/genetics , Macrophages/metabolism , Colorectal Neoplasms/pathology , Fatty Acids/metabolism , Tumor Microenvironment , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , AlkB Homolog 5, RNA Demethylase/genetics , AlkB Homolog 5, RNA Demethylase/metabolism
8.
Curr Pharm Des ; 30(12): 952-967, 2024.
Article in English | MEDLINE | ID: mdl-38482629

ABSTRACT

INTRODUCTION: Although anthracyclines have demonstrated efficacy in cancer therapy, their utilization is constrained by cardiotoxicity. In contrast, Danshen injection (DSI), derived from Salvia miltiorrhiza, has a longstanding tradition of being employed to ameliorate cardiovascular ailments, including anthracycline- induced cardiotoxicity (AIC). Nonetheless, there is a notable dearth of comprehensive systematic investigation into the molecular mechanisms underlying DSI's effects on AIC. Consequently, this study was undertaken to explore the underlying mechanism by which DSI acted against AIC. METHODS: Employing network pharmacology approach, the current investigation undertook a comprehensive analysis of the impact of DSI on AIC, which was further validated by transcriptome sequencing with in vitro AIC model. Additionally, molecular docking was conducted to evaluate the binding of active ingredients to core targets. A total of 3,404 AIC-related targets and 12 active ingredients in DSI, including chrysophanol, luteolin, tanshinone IIA, isoimperatorin, among others, were collected by differentially expressed analysis and database search, respectively. RESULTS: The network pharmacology and enrichment analysis suggested 102 potential targets and 29 signaling pathways associated with the protective effect of DSI on AIC. Three core targets (CA12, NOS3, and POLH) and calcium signaling pathways were further validated by transcriptomic analysis of the in-vitro model. The high affinity of the active ingredients binding to corresponding targets was confirmed by molecular docking. CONCLUSION: The present study suggested that DSI might exert a cardioprotective effect on AIC via the inhibition of CA12, NOS3, and POLH, as well as the modulation of calcium signaling. Further experiments are warranted to verify the findings.


Subject(s)
Cardiotoxicity , Drugs, Chinese Herbal , Molecular Docking Simulation , Network Pharmacology , Salvia miltiorrhiza , Transcriptome , Salvia miltiorrhiza/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Transcriptome/drug effects , Cardiotoxicity/prevention & control , Cardiotoxicity/metabolism , Humans , Anthracyclines/chemistry , Anthracyclines/adverse effects , Animals
9.
Rapid Commun Mass Spectrom ; 38(9): e9719, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38500352

ABSTRACT

RATIONALE: As 3-OH-containing steroids are prone to dehydration by conventional electrospray ionization, reducing detection sensitivity, Li ion adduction-based ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS), developed to prevent dehydration and effectively detect 3-OH steroids, was applied for profiling total and free steroids in urine. METHODS: Free urinary steroids were isolated directly from urine by solid-phase extraction (SPE) with 80% acetonitrile. The total steroids were prepared by enzymatic treatment of urine with a cocktail of sulfatase and glucronidase, protein precipitation, and separation with the above SPE. In order to detect as many steroid types as possible, UHPLC/MS/MS (Li method) with Li+ solution added after the column was used for analysis in addition to the conventional method of detecting protonated ions (H method). The 13 3-OH steroids and the remaining 16 steroids were quantified by standard curves prepared using product ion transitions derived from [M + Li]+ and MH+ , respectively. RESULTS: Two groups of human urine, male and female urine, were analyzed. 3-OH steroids could be detected with greater sensitivity using the Li method than the conventional method. The absolute amounts of each steroid were normalized based on creatinine levels. The difference between the male and female groups are clearly attributable to sex steroids. CONCLUSIONS: Twenty-nine total steroids and 19 free steroids were identified in a limited volume (240 mL) of urine. Of these, 13 3-OH steroids were better detected by Li+ adduction-based UHPLC/MS/MS.


Subject(s)
Lithium , Tandem Mass Spectrometry , Male , Female , Humans , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Dehydration , Steroids/urine , Ions
10.
Front Nutr ; 11: 1344924, 2024.
Article in English | MEDLINE | ID: mdl-38549744

ABSTRACT

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a significant global health concern, representing a major cause of liver disease worldwide. This condition spans a spectrum of histopathologic stages, beginning with simple fatty liver (MAFL), characterized by over 5% fat accumulation, and advancing to metabolic (dysfunction)-associated steatohepatitis, potentially leading to hepatocellular carcinoma. Despite extensive research, there remains a substantial gap in effective therapeutic interventions. This condition's progression is closely tied to micronutrient levels, crucial for biological functions like antioxidant activities and immune efficiency. The levels of these micronutrients exhibit considerable variability among individuals with MAFLD. Moreover, the extent of deficiency in these nutrients can vary significantly throughout the different stages of MAFLD, with disease progression potentially exacerbating these deficiencies. This review focuses on the role of micronutrients, particularly vitamins A, D, E, and minerals like iron, copper, selenium, and zinc, in MAFLD's pathophysiology. It highlights how alterations in the homeostasis of these micronutrients are intricately linked to the pathophysiological processes of MAFLD. Concurrently, this review endeavors to harness the existing evidence to propose novel therapeutic strategies targeting these vitamins and minerals in MAFLD management and offers new insights into disease mechanisms and treatment opportunities in MAFLD.

11.
Adv Mater ; : e2313986, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38507727

ABSTRACT

As hydrodynamic metamaterials continue to develop, the inherent limitations of passive-mode metamaterials become increasingly apparent. First, passive devices are typically designed for specific environments and lack the adaptability to environmental changes. Second, their unique functions often rely on intricate structures, or challenging material properties, or a combination of both. These limitations considerably hinder the potential applications of hydrodynamic metamaterials. In this study, an active-mode hydrodynamic metamaterial is theoretically proposed and experimentally demonstrated by incorporating source-and-sink flow-dipoles into the system, enabling active manipulation of the flow field with various functionalities. By adjusting the magnitude and direction of the flow-dipole moment, this device can easily achieve invisibility, flow shielding, and flow enhancing. Furthermore, it is environmentally adaptive and can maintain proper functions in different environments. It is anticipated that this design will significantly enhance tunability and adaptability of hydrodynamic metamaterials in complex and ever-changing environments.

12.
Pharmacol Res ; 202: 107124, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38428704

ABSTRACT

Metabolic syndrome has become major health problems in recent decades, and natural compounds receive considerable attention in the management of metabolic syndrome. Among them, naringin is abundant in citrus fruits and tomatoes. Many studies have investigated the therapeutic effects of naringin in metabolic syndrome. This review discusses in vitro and in vivo studies on naringin and implications for clinical trials on metabolic syndrome such as diabetes mellitus, obesity, nonalcoholic fatty liver disease, dyslipidemia, and hypertension over the past decades, overviews the molecular mechanisms by which naringin targets metabolic syndrome, and analyzes possible correlations between the different mechanisms. This review provides a theoretical basis for the further application of naringin in the treatment of metabolic syndrome.


Subject(s)
Flavanones , Metabolic Syndrome , Non-alcoholic Fatty Liver Disease , Humans , Metabolic Syndrome/drug therapy , Metabolic Syndrome/metabolism , Flavanones/pharmacology , Flavanones/therapeutic use , Obesity/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy
13.
RSC Adv ; 14(12): 8090-8099, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38464692

ABSTRACT

Deep eutectic solvents (DESs) are considered one of the most promising biomass pretreatment reagents, and their research applications in woody fibrous biomass are increasing yearly. Inspired by the research related to wood bending, we explored the effects of different DES systems on the bending development of wood, and the results showed that the addition of anhydrous ferric trichloride to the DES system of lactic acid/choline chloride could enhance the treatment effect that increased the bendability and torsion resistance of ash wood. The anhydrous FeCl3 could act as an active site and provide acidic protons to improve the treatment efficiency of DES. In addition, the addition of an appropriate amount of water can reduce the viscosity of the DES system, and the highest lignin removal rate was obtained at 10 wt% of water in the DES, which resulted in the best mechanical properties and tensile resilience of ash wood, with the tensile strength and stability of 97 MPa and 13.6%, respectively, as determined by experiments with different water contents in different mass fractions. Therefore, using a DES can effectively improve the bending properties of wood.

14.
Future Oncol ; 20(3): 121-129, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38353107

ABSTRACT

Immune checkpoint inhibitors (ICIs) plus chemotherapy has demonstrated efficacy in resectable non-small-cell lung cancer (NSCLC), yet the optimal period of neoadjuvant immunochemotherapy is undetermined. In a phase II study (neoSCORE, NCT04459611), more neoadjuvant therapy cycles appeared to provide greater pathological remission, and patients with squamous NSCLC had a better major pathological response rate than those with nonsquamous NSCLC. Sintilimab, a monoclonal anti-PD-1 antibody, has shown encouraging antitumor activity and safety in multiple cancers, including NSCLC. Here, we describe the study design of neoSCORE II (NCT05429463), a randomized, open-label, multicenter phase III trial comparing the efficacy and safety of three cycles with four cycles of neoadjuvant sintilimab plus platinum-based chemotherapy in resectable stage IIA-IIIB squamous NSCLC. Trial registration number: NCT05429463 (ClinicalTrials.gov).


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Neoadjuvant Therapy , Lung Neoplasms/drug therapy , Carcinoma, Squamous Cell/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as Topic
15.
Theor Appl Genet ; 137(1): 7, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38093101

ABSTRACT

KEY MESSAGE: A novel light-dependent dominant lesion mimic mutant with enhanced multiple disease resistance was physiologically, biochemically, and genetically characterized; the causal gene was fine mapped to a 909 kb interval containing 38 genes. Identification of genes that confer multiple disease resistance (MDR) is crucial for the improvement of maize disease resistance. However, very limited genes are identified as MDR genes in maize. In this study, we characterized a dominant disease lesion mimics 8 (Les8) mutant that had chlorotic lesions on the leaves and showed enhanced resistance to both curvularia leaf spot and southern leaf blight. Major agronomic traits were not obviously altered, while decreased chlorophyll content was observed in the mutant, and the genetic effect of the Les8 mutation was stable in different genetic backgrounds. By BSR-seq analysis and map-based cloning, the LES8 gene was mapped into a 909 kb region containing 38 candidate genes on chromosome 9 wherein no lesion mimic or disease-resistance genes were previously reported. Using transcriptomics analysis, we found that genes involved in defense responses and secondary metabolite biosynthesis were enriched in the significantly up-regulated genes, while genes involved in photosynthesis and carbohydrate-related pathways were enriched in the significantly down-regulated genes in Les8. In addition, there was an overaccumulation of jasmonic acid and lignin but not salicylic acid in Les8. Taken together, this study revealed candidate genes and potential mechanism underlying Les8-conferred MDR in maize.


Subject(s)
Curvularia , Zea mays , Chromosome Mapping , Curvularia/genetics , Zea mays/genetics , Disease Resistance/genetics , Genes, Plant , Plant Leaves/genetics , Plant Diseases/genetics
16.
Front Nutr ; 10: 1301129, 2023.
Article in English | MEDLINE | ID: mdl-38099180

ABSTRACT

Prediabetes is an intermediate stage in the development of type 2 diabetes mellitus characterized by impaired fasting glucose and/or impaired glucose tolerance. Prediabetes generally has no obvious clinical symptoms, and most patients are found in health examinations or due to other diseases. Reactive hypoglycemia may indicate the possibility of early diabetes. Without effective preventive measures, prediabetes can progress to diabetes leading to serious public health problems. Therefore, early diagnosis and intervention are important. Many animal experiments and clinical trials have proven that natural compounds substantially improve glucose metabolism disorder. The active ingredients are mainly alkaloids, polysaccharides, saponins, terpenoids, flavonoids and polyphenols. Their mechanism of action mainly involves improved insulin sensitivity and insulin resistance, inhibited activity of alpha-glucosidase, antioxidant activity, anti-inflammatory, regulation of gut microbiota and activating of peroxisome proliferator-activated receptor-γ. This paper reviews the mechanisms of action of natural compounds on prediabetes and the status of related research.

17.
Insights Imaging ; 14(1): 160, 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37755551

ABSTRACT

OBJECTIVE: To investigate the pelvic floor changes in primiparas with postpartum stress urinary incontinence (SUI) after vaginal delivery using pelvic floor MRI. MATERIALS AND METHODS: Fifty-two women were enrolled in the primiparous stress urinary incontinent (PSUI) group and 51 in the primiparous continent (PC) group. Thirty nulliparas were also recruited as the nulliparous control (NC) group. Levator ani muscle (LAM) injury, levator hiatus area (LHA), H-line, M-line, the distance from the bladder neck and cervix to the pubococcygeal line (B-PCL and U-PCL), levator plate angle, the anterior angle of the urethra, bladder neck descent, retrovesicourethral angle, functional urethral length, and a bladder neck funnel were evaluated on MRI images. Univariate and multivariate logistic regression analyses were used to explore anatomical predictors for SUI. RESULTS: The primiparas in the PSUI group showed more obvious LAM injuries than in the PC groups (p = 0.001). LAM function assessment: the PSUI group had larger LHA and shorter B-PCL and U-PCL than the other groups during straining. Assessment of urethral mobility and function: the PSUI group had larger anterior angle of the urethra, bladder neck descent, retrovesicourethral angle, and shorter functional urethral length than the other two groups (all p < 0.05). Up to 88.5% of primiparas in the PSUI group showed bladder funnel (p < 0.001). The logistic regression analysis showed that retrovesicourethral angle, functional urethral length, and the presence of bladder funnel were significantly associated with postpartum SUI (p < 0.05). CONCLUSIONS: Increased retrovesicourethral angle, shortened functional urethral length, and the presence of bladder funnel may be anatomical predictors for SUI in the early postpartum period. Urethral sphincter dysfunction plays an essential role in developing postpartum SUI. CRITICAL RELEVANCE STATEMENT: This study used several measurements to reflect the anatomical structure and functional changes of the pelvic floor to identify the best anatomical predictors associated with postpartum stress urinary incontinence (SUI), aiming to provide new insights into treatment strategies for postpartum SUI. KEY POINTS: • Increased retrovesicourethral angle, shortened functional urethral length, and the presence of bladder funnel are more commonly seen in primiparas with SUI. • The combination of retrovesicourethral angle, functional urethral length, and bladder funnel had the highest diagnostic performance in predicting postpartum SUI (AUC=0.947). • Urethral sphincter dysfunction may be the main pathophysiological foundation in SUI development.

18.
RSC Adv ; 13(32): 22569-22578, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37501779

ABSTRACT

Cellulose nanocrystals (CNC) possess remarkable mechanical properties, a high aspect ratio, a large specific surface area, and a unique nanostructure, making them a popular choice in various fields. In this study, a CNC suspension was prepared through acid hydrolysis, and subsequently, a film exhibiting iridescence and chiral nematic structure was formed on the cured UV-WA surface via evaporation-induced self-assembly. The mean diameter and length of CNC were determined to be 25.1-33.3 nm and 281.3-404.2 nm, respectively, through transmission electron microscope analysis. The experimental results revealed that the color of the film significantly changes with variations in the CNC suspension concentration. Notably, the formation of the iridescent film is dependent on the concentration of CNC, with concentrations between 1.2% and 2.9% being optimal, and the aspect ratio of the CNC nanoparticles being around 11.3. X-ray diffraction analysis confirmed that the CNC nanoparticles possess the same crystal structure as microcrystalline cellulose (cellulose I). Fourier transform infrared spectroscopy revealed that the C[double bond, length as m-dash]C bond present in the liquid UV-curable coating disappeared upon UV irradiation. The performance of the CNC iridescent film, with varying thickness, was evaluated using UV-vis spectroscopy. The thermogravimetric analysis results indicate that the addition of CNC enhances the membrane's thermal stability and heat resistance. The results indicate that as the thickness of the CNC iridescent film increases, the corresponding UV-vis spectra display a redshift. The UV-WA/CNC shows potential in the field of decoration and establishing a straightforward, cost-effective, and efficient method for producing photonic materials with structural colors.

19.
Adv Healthc Mater ; 12(28): e2301328, 2023 11.
Article in English | MEDLINE | ID: mdl-37392128

ABSTRACT

To strengthen the antitumor efficacy and avoid toxicity to normal cells of cisplatin and triptolide, herein, an acid and glutathione (GSH) dual-controlled nanoplatform for enhanced cancer treatment through the synergy of both "1+1" apoptosis and "1+1" ferroptosis is designed. Remarkably, ZIF8 in response to tumor microenvironment enhances drug targeting and protects drugs from premature degradation. Meanwhile, the PtIV  center can be easily reduced to cisplatin because of the large amount of GSH, thus liberating the triptolide as the coordinated ligand. The released cisplatin and hemin in turn boost the tumor cell "1+1" apoptosis through chemotherapy and photodynamic therapy, respectively. Furthermore, GSH reduction through PtIV  weakens the activation of glutathione peroxidase 4 (GPX4) effectively. The released triptolide can inhibit the expressions of GSH by regulating nuclear factor E2 related factor 2 (Nrf2), further promoting membrane lipid peroxidation, thus "1+1" ferroptosis can be achieved. Both in vitro and in vivo results demonstrate that the nanosystem can not only perform superior specificity and therapeutic outcomes but also reduce the toxicity to normal cells/tissues of cisplatin and triptolide effectively. Overall, the prodrug-based smart system provides an efficient therapeutic strategy for cancer treatment by virtue of the effect of enhanced "1+1" apoptosis and "1+1" ferroptosis therapies.


Subject(s)
Breast Neoplasms , Diterpenes , Prodrugs , Humans , Female , Cisplatin/pharmacology , Breast Neoplasms/drug therapy , Prodrugs/pharmacology , Cell Line, Tumor , Tumor Microenvironment
20.
Heliyon ; 9(5): e16160, 2023 May.
Article in English | MEDLINE | ID: mdl-37234613

ABSTRACT

The development of a country is inseparable from the material guarantee mainly based on energy, but energy is limited, which may restrict the sustainable development of the country. It is very necessary to accelerate the adoption of programs aimed at switching non-renewable energy sources to ones that are, and giving priority to improving renewable energy consumption and storage capabilities. From the experience of the G7 economies, the development of renewable energy (RE) is inevitable and urgent. The China Banking Regulatory Commission has recently issued a number of directives, such as the "Directives for Green Credit" and "Instructions for Granting Credit to Support Energy Conservation and Emission Reduction," to help businesses that use "renewable energy expand". This article firstly discussed the definition of the "green institutional environment" (GIE) and the construction of the index system. Then, on the basis of clarifying the relationship between the GIE, and RE investment theory, a semi-parametric regression model was constructed to empirically analyze the mode and effect of the GIE. Considering the balance between improving model accuracy and reducing computational complexity, the number of hidden nodes opted in this study is 300 so as to lower the time needed to predict the model. Finally, from the perspective of enterprise scale, the level of GIE played a significant role in promoting RE investment in small and medium-sized enterprises, with a coefficient of 1.8276, while the impact on RE investment in large enterprises had not passed the significance test. Based on the conclusions, the government should focus on building a GIE dominated by green regulatory systems, supplemented by green disclosure and supervision systems, and green accounting systems, and should make reasonable plans for releasing various policy directives. At the same time, while offering full play to the guiding role of the policy, its rationality should also be paid attention to, and the excessive implementation of the policy should be avoided, so that an orderly, and good GIE can be created.

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