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1.
J Environ Sci (China) ; 148: 263-273, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39095162

ABSTRACT

The adsorption of pollutants can not only promote the direct surface reaction, but also modify the catalyst itself to improve its photoelectric characteristics, which is rarely studied for water treatment with inorganic photocatalyst. A highly crystalline BiOBr (c-BiOBr) was synthesized by a two-step preparation process. Owing to the calcination, the highly crystalline enhanced the interface interaction between pollutant and c-BiOBr. The complex of organic pollutant and [Bi2O2]2+ could promote the active electron transfer from the adsorbed pollutant to c-BiOBr for the direct pollutant degradation by holes (h+). Moreover, the pollutant adsorption actually modified c-BiOBr and promoted more unpaired electrons, which would coupling with the photoexcitation to promote generate more O2•-. The molecular modification effect derived from pollutant adsorption significantly improved the removal of pollutants. This work strongly deepens the understanding of the molecular modification effect from the pollutant adsorption and develops a novel and efficient approach for water treatment.


Subject(s)
Water Pollutants, Chemical , Adsorption , Water Pollutants, Chemical/chemistry , Catalysis , Bismuth/chemistry , Water Purification/methods
2.
Article in English | MEDLINE | ID: mdl-39265038

ABSTRACT

Industrial processes generate huge volumes of oily saline wastewater. Instead of being sent to the drainage system immediately, extracting osmotic energy from these effluents represents a promising means to reuse these wastes and contributes to mitigate the ever-growing energy crisis. Herein, an MOF-decorated PTFE membrane is engineered to extract osmotic energy from oily wastewaters. Copper hydroxide nanowires (CHNs) are intertwined with polystyrenesulfonate sodium (PSS), deposited onto a poly(tetrafluoroethylene) (PTFE) membrane, and thereafter used as metal precursors to in situ generate HKUST-1 doped with negative charges. The resulting HKUST-1PSS@PTFE hybrid membrane possesses abundant angstrom-scale channels capable of transporting cations efficiently and features a hierarchically structured surface with underwater superoleophobicity. The energy conversion performance of the HKUST-1PSS3.5@PTFE membrane can reach an output power density of 6.21 W m-2 at a 50-fold NaCl gradient, which is superior to those of pristine PTFE membranes. Once exposed to oily saline wastewater, the HKUST-1PSS@PTFE membrane can exhibit an excellent oil-repellent ability, thus contributing to sustain its osmotic energy harvesting. This work may promote the development of antifouling osmotic energy harvesters with a long working life and pave the way to fully exploit oily wastewater effluents as valuable energy sources.

3.
iScience ; 27(9): 110758, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39280613

ABSTRACT

Osteosarcoma, the most prevalent malignant bone tumor, is notorious for its aggressive growth and invasiveness. The highly mutable genome of osteosarcoma has made identifying a key oncogene challenging, hindering the development of targeted treatments. Our study validates the effectiveness of XD23, an anti-cancer agent we previously identified, in curbing osteosarcoma proliferation, metastasis, EMT differentiation, and bone destruction and promoting osteosarcoma apoptosis. It further elucidated that XD23 thwarts osteosarcoma by suppressing DKK1 expression, which in turn activates the WNT-ß/Catenin pathway. This research presents the concrete evidence of DKK1's involvement in osteosarcoma development, offering a foundation for the development of DKK1 inhibitors as novel treatments for this disease.

4.
J Fish Biol ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235098

ABSTRACT

In fish species, there is limited analysis of signature transcriptome profiles at the single-cell level in gonadal cells. Here, the molecular signatures of distinct ovarian cell categories in adult Nile tilapia (Oreochromis niloticus) were analysed using single-nucleus RNA sequencing (snRNA-seq). We identified four cell types (oogonia, oocytes, granulosa cell, and thecal cell) based on their specifically expressed genes and biological functions. Similarly, we found some key pathways involved in ovarian development that may affect germline-somatic interactions. A cell-to-cell communication network between the distinct cell types was constructed. We found that the bidirectional communication is mandatory for the development of germ cells and somatic cells in fish ovaries, and the granulosa cells and thecal cells play a central regulating role in the cell network in fish ovary. Additionally, we identified some novel candidate marker genes for various types of ovarian cells and also validated them using in situ hybridization. Our work reveals an ovarian atlas at the cellular and molecular levels and contributes to providing insights into oogenesis and gonad development in fish.

5.
Transl Cancer Res ; 13(8): 4315-4323, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39262466

ABSTRACT

Background: Pancreatic neuroendocrine neoplasm (pNEN) poses significant challenges in clinical management due to their heterogeneity and limited treatment options. In this study, we investigated the potential of simvastatin (SIM) as an anti-tumor agent in pNEN. Methods: We conducted cell culture experiments using QGP-1 and BON-1 cell lines and assessed cell viability, proliferation, migration, and invasion following SIM treatment. To further validate our findings, we performed in vivo experiments using a mouse xenograft model. Additionally, we investigated the underlying molecular mechanisms by analyzing changes in cell cycle progression, apoptosis, and signaling pathways. Results: SIM treatment suppresses pNEN growth both in vitro and in vivo, and led to G1 phase arrest in QGP-1 cells. In contrast, SIM affected both the G1-S and G2-M phase transitions in the BON-1 cell line and induced apoptosis, indicating diverse mechanisms of action. Furthermore, SIM treatment resulted in decreased expression of mutant p53 (mutp53) in BON-1 cells, suggesting a potential therapeutic strategy targeting mutp53. Modulation of the MAPK pathway was also implicated in QGP-1 cells. Conclusions: Our study highlights SIM as a promising candidate for pNEN treatment by inducing cell cycle arrest or apoptosis, potentially through the p53 and MAPK pathways. Further research is warranted to fully elucidate SIM's mechanisms of action and evaluate its therapeutic potential in clinical settings.

6.
BMC Med Imaging ; 24(1): 211, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39134943

ABSTRACT

BACKGROUND: To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP). METHODS: A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups. RESULTS: In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups. CONCLUSIONS: Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery.


Subject(s)
Carcinoma, Hepatocellular , Contrast Media , Focal Nodular Hyperplasia , Gadolinium DTPA , Liver Neoplasms , Magnetic Resonance Imaging , Nomograms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Female , Male , Focal Nodular Hyperplasia/diagnostic imaging , Middle Aged , Magnetic Resonance Imaging/methods , Diagnosis, Differential , Adult , Aged , Retrospective Studies , ROC Curve
7.
Science ; 385(6708): 554-560, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39088618

ABSTRACT

Wide-bandgap (WBG) absorbers in tandem configurations suffer from poor crystallinity and weak texture, which leads to severe mixed halide-cation ion migration and phase segregation during practical operation. We control WBG film growth insensitive to compositions by nucleating the 3C phase before any formation of bromine-rich aggregates and 2H phases. The resultant WBG absorbers show improved crystallinity and strong texture with suppressed nonradiative recombination and enhanced resistance to various aging stresses. Perovskite/silicon tandem solar cells achieve power conversion efficiencies of 29.4% (28.8% assessed by a third party) in a 25-square centimeter active area and 32.5% in a 1-square centimeter active area. These solar cells retained 98.3 and 90% of the original efficiency after 1301 and 800 hours of operation at 25° and 50°C, respectively, at the maximum power point (AM 1.5G illumination, full spectrum, 1-sun) when encapsulated.

8.
Foods ; 13(15)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39123519

ABSTRACT

Rice bran, a byproduct of rice milling, comprises 12-14% protein. The foaming properties and associated mechanisms of the composite rice bran protein system were not well studied. In this study, a composite protein system composed of rice bran protein (RBP)-sodium caseinate (NaCas) and rice bran protein nanoparticles (RBPNs)-sodium caseinate (NaCas) was investigated. The results showed that the synergistic effect of RBP and NaCas increased the foaming stability of the composite solution up to 83.77 ± 2.75%. Moreover, the foaming capacity and foaming stability of the RBPNs-NaCas composite solution were up to 177.50 ± 3.53% and 80.28 ± 0.39%, respectively. The physicochemical properties results revealed that the particle size volume peaks of RBP-NaCas and RBPNs-NaCas were mainly concentrated at 55.7 nm and 197.1 nm, and RBPNs-NaCas showed a wider single peak particle size distribution. The ζ-potential values of RBP-NaCas and RBPNs-NaCas were changed to -35.5 ± 0.07 mV and -27.2 ± 0.28 mV after complexation. The apparent viscosity and consistency factor of RBP-NaCas decreased by 31.1% compared to RBP, while RBPNs-NaCas displayed similar parameters to the single proteins. The interfacial rheological test showed that RBP and RBPNs can significantly improve the interfacial properties of NaCas by enhancing the interfacial interaction and the interfacial viscoelastic modulus of composite proteins, which is conducive to the stability of the foam system. The outcome of the study provided a theoretical basis for RBP and RBPNs to partially replace NaCas in the processing of foamed food.

9.
Biochem Biophys Res Commun ; 732: 150406, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-39032412

ABSTRACT

Lignocellulose, the most abundant organic waste on Earth, is of economic value because it can be converted into biofuels like ethanol by enzymes such as ß-glucosidase. This study involved cloning a ß-glucosidase gene named JBG from the rumen fungus Neocallimastix patriciarum J11. When expressed recombinantly in Escherichia coli, the rJBG enzyme exhibited significant activity, hydrolyzing 4-nitrophenyl-ß-d-glucopyranoside and cellobiose to release glucose. Surprisingly, the rJBG enzyme also showed hydrolytic activity against ß-glucan, breaking it down into glucose, indicating that the rJBG enzyme possesses both ß-glucosidase and ß-glucanase activities, a characteristic rarely found in ß-glucosidases. When the JBG gene was expressed in Saccharomyces cerevisiae and the transformants were inoculated into a medium containing ß-glucan as the sole carbon source, the ethanol concentration in the culture medium increased from 0.17 g/L on the first day to 0.77 g/L on the third day, reaching 1.3 g/L on the fifth day, whereas no ethanol was detected in the yeast transformants containing the recombinant plasmid pYES-Sur under the same conditions. These results demonstrate that yeast transformants carrying the JBG gene can directly saccharify ß-glucan and ferment it to produce ethanol. This gene, with its dual ß-glucosidase and ß-glucanase activities, simplifies and reduces the cost of the typical process of converting lignocellulose into bioethanol using enzymes and yeast.


Subject(s)
Neocallimastix , Recombinant Proteins , beta-Glucosidase , beta-Glucosidase/genetics , beta-Glucosidase/metabolism , Recombinant Proteins/metabolism , Recombinant Proteins/genetics , Animals , Neocallimastix/genetics , Neocallimastix/metabolism , Neocallimastix/enzymology , Rumen/microbiology , Cloning, Molecular , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , beta-Glucans/metabolism , Ethanol/metabolism , Lignin/metabolism
10.
iScience ; 27(7): 110219, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39021795

ABSTRACT

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

12.
J Environ Sci (China) ; 146: 55-66, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38969462

ABSTRACT

The effects of cast iron pipe corrosion on water quality risk and microbial ecology in drinking water distribution systems (DWDSs) were investigated. It was found that trihalomethane (THMs) concentration and antibiotic resistance genes (ARGs) increased sharply in the old DWDSs. Under the same residual chlorine concentration conditions, the adenosine triphosphate concentration in the effluent of old DWDSs (Eff-old) was significantly higher than that in the effluent of new DWDSs. Moreover, stronger bioflocculation ability and weaker hydrophobicity coexisted in the extracellular polymeric substances of Eff-old, meanwhile, iron particles could be well inserted into the structure of the biofilms to enhance the mechanical strength and stability of the biofilms, hence enhancing the formation of THMs. Old DWDSs significantly influenced the microbial community of bulk water and triggered stronger microbial antioxidant systems response, resulting in higher ARGs abundance. Corroded cast iron pipes induced a unique interaction system of biofilms, chlorine, and corrosion products. Therefore, as the age of cast iron pipes increases, the fluctuation of water quality and microbial ecology should be paid more attention to maintain the safety of tap water.


Subject(s)
Biofilms , Iron , Water Quality , Water Supply , Corrosion , Water Microbiology , Drinking Water/microbiology , Drinking Water/chemistry , Drug Resistance, Microbial/genetics , Environmental Monitoring , Water Pollutants, Chemical/analysis , Trihalomethanes/analysis
13.
Eur Radiol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38987399

ABSTRACT

OBJECTIVE: To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS: The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION: Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT: The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS: Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.

14.
Commun Biol ; 7(1): 843, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987326

ABSTRACT

Bcr-Abl transformation leads to chronic myeloid leukemia (CML). The acquirement of T315I mutation causes tyrosine kinase inhibitors (TKI) resistance. This study develops a compound, JMF4073, inhibiting thymidylate (TMP) and cytidylate (CMP) kinases, aiming for a new therapy against TKI-resistant CML. In vitro and in vivo treatment of JMF4073 eliminates WT-Bcr-Abl-32D CML cells. However, T315I-Bcr-Abl-32D cells are less vulnerable to JMF4073. Evidence is presented that ATF4-mediated upregulation of GSH causes T315I-Bcr-Abl-32D cells to be less sensitive to JMF4073. Reducing GSH biosynthesis generates replication stress in T315I-Bcr-Abl-32D cells that require dTTP/dCTP synthesis for survival, thus enabling JMF4073 susceptibility. It further shows that the levels of ATF4 and GSH in several human CML blast-crisis cell lines are inversely correlated with JMF4073 sensitivity, and the combinatory treatment of JMF4073 with GSH reducing agent leads to synthetic lethality in these CML blast-crisis lines. Altogether, the investigation indicates an alternative option in CML therapy.


Subject(s)
Glutathione , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Glutathione/metabolism , Humans , Animals , Mice , Protein Kinase Inhibitors/pharmacology , Drug Resistance, Neoplasm/drug effects , Cell Line, Tumor , Fusion Proteins, bcr-abl/metabolism , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/antagonists & inhibitors
15.
Front Nutr ; 11: 1409339, 2024.
Article in English | MEDLINE | ID: mdl-39070259

ABSTRACT

Considering a growing, aging population, the need for interventions to improve the healthspan in aging are tantamount. Diet and nutrition are important determinants of the aging trajectory. Plant-based diets that provide bioactive phytonutrients may contribute to offsetting hallmarks of aging and reducing the risk of chronic disease. Researchers now advocate moving toward a positive model of aging which focuses on the preservation of functional abilities, rather than an emphasis on the absence of disease. This narrative review discusses the modulatory effect of nutrition on aging, with an emphasis on promising phytonutrients, and their potential to influence cellular, organ and functional parameters in aging. The literature is discussed against the backdrop of a recent conceptual framework which describes vitality, intrinsic capacity and expressed capacities in aging. This aims to better elucidate the role of phytonutrients on vitality and intrinsic capacity in aging adults. Such a review contributes to this new scientific perspective-namely-how nutrition might help to preserve functional abilities in aging, rather than purely offsetting the risk of chronic disease.

17.
Environ Res ; 259: 119554, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38964571

ABSTRACT

Hospital wastewaters (HWWs) serve as critical reservoirs for disseminating antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB). However, the dynamics and noteworthy shifts of ARGs and their associated pathogenicity, mobility, and resistome risks during HWWs treatment processes remain poorly understood. Utilizing metagenomic sequencing and assembly, we identified 817 ARG subtypes conferring resistance to 20 classes of antibiotics across 18 HWW samples from influent to effluent. Genes encoding resistance to multidrug, aminoglycoside and beta_lactam were the most prevalent ARG types, reflecting patterns observed in clinical settings. On-site treatment efforts decreased the relative abundance of ARGs by 77.4% from influent to secondary sedimentation, whereas chlorine disinfection significantly increased their abundance in the final effluent. Deterministic processes primarily drove the taxonomic assembly, with Proteobacteria being the most abundant phylum and serving as the primary host for 15 ARG types. Contig-based analysis further revealed 114 pathogenic ARB, with Escherichia coli, Pseudomonas alcaligenes, and Pseudomonas aeruginosa exhibiting multidrug-resistant. The contributions of host bacteria and pathogenic ARB varied throughout wastewater treatment. In addition, 7.10%-31.0 % ARGs were flanked by mobile genetic elements (MGEs), predominantly mediated by transposase (74.1%). Notably, tnpA exhibited the highest potential for ARG dissemination, frequently co-occurring with beta-lactam resistance genes (35.2%). Considering ARG profiles, pathogenic hosts, and transferability, raw influent exhibited the highest antibiotic resistome risk index (ARRI), followed by the final effluent. Chlorine disinfection exacerbated resistome risks by inducing potential pathogenic ARB and mobile ARGs, posing threats to the receiving environment. This study delineates ARG occurrence patterns, highlights mechanisms of ARG carriage and horizontal gene transfer, and provides insights for assessing resistance risks and prioritizing interventions in clinical settings.


Subject(s)
Hospitals , Wastewater , Wastewater/microbiology , Waste Disposal, Fluid , Bacteria/genetics , Bacteria/drug effects , Bacteria/pathogenicity , Anti-Bacterial Agents/pharmacology , Genes, Bacterial , Drug Resistance, Microbial/genetics , Drug Resistance, Bacterial/genetics
18.
Int J Biol Macromol ; 276(Pt 1): 133489, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38964679

ABSTRACT

Indole-based bis-acylhydrazone compounds can inhibit the activity of α-glucosidase and control the concentration of blood glucose. In this paper, the characteristics of three indole-based bis-acylhydrazone compounds with different inhibitory activities of α-glucosidase as well as the interaction with α-glucosidase were studied by experiments and computational simulation techniques. Enzyme kinetic and spectral experiments showed that the indole-based bis-acylhydrazone compounds were able to inhibit enzyme activity through mixed inhibition dominated by competitive inhibition, and during the binding reaction, indole-based bis-acylhydrazone compounds can quench the intrinsic fluorescence of α-glucosidase through static quenching and an aggregation of the indole-based bis-acylhydrazone with α-glucosidase produces a stable complex with a molar ratio of 1:1, and the combination of indole-based bis-acylhydrazone compounds could lead to slight change in the conformation of α-glucosidase. The theoretical simulation demonstrated that the stability of the complex systems was positively correlated with the inhibitory activity of indole-based bis-acylhydrazone compounds, and the indole-based bis-acylhydrazone compounds occupied the active site in the multi-ligand system, resulting in a significant decrease in the binding ability of starch to active amino acids. These results suggested that indole-based bis-acylhydrazone compound was expected to be a new type of α-glucosidase inhibitor.


Subject(s)
Glycoside Hydrolase Inhibitors , Hydrazones , Indoles , alpha-Glucosidases , alpha-Glucosidases/metabolism , alpha-Glucosidases/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Indoles/chemistry , Indoles/pharmacology , Hydrazones/chemistry , Hydrazones/pharmacology , Kinetics , Molecular Docking Simulation , Spectrum Analysis
19.
iScience ; 27(7): 110346, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39055920

ABSTRACT

Over 80% of the patients with pancreatic ductal adenocarcinoma (PDAC) have cachexia/wasting syndrome. Cachexia is associated with reduced survival, decreased quality of life, and higher metastasis rates. Here, we demonstrate that fat loss is the earliest feature of PDAC-exosome-induced cachexia. MicroRNA sequencing of exosomal components from normal and cancer-derived exosomes revealed enrichment of miR-16-5p, miR-21-5p, miR-29a-3p, and miR-125b-5p in serum exosomes of mice harboring PDAC and patients with PDAC. Further, miR-16-5p and miR-29a-3p inhibited adipogenesis through decreasing Erlin2 and Cmpk1 expression which downregulates C/EBPß and PPARγ. Synergistically, miR-29a-3p promotes lipolysis through increasing ATGL expression by suppressing MCT1 expression. Furthermore, PDAC-exosomes deprived of miR-16-5p and miR-29a-3p fail to induce fat loss. Hence, miR-16-5p and miR-29a-3p exosomal miRs are essential for PDAC-induced fat loss. Thus, we unravel that PDAC induces adipose atrophy via exosomal miRs. This knowledge may provide new diagnostic and therapeutic strategies for PDAC-induced cachexia.

20.
Nat Commun ; 15(1): 5879, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-38997253

ABSTRACT

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.


Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Xanthenes , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Xanthenes/chemical synthesis , Xanthenes/pharmacology , Xanthenes/chemistry , Microbial Sensitivity Tests , Stereoisomerism , Polycyclic Compounds/chemical synthesis , Polycyclic Compounds/pharmacology , Polycyclic Compounds/chemistry , Drug Discovery , Molecular Structure
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