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1.
Carbohydr Polym ; 346: 122570, 2024 Dec 15.
Article in English | MEDLINE | ID: mdl-39245477

ABSTRACT

This study investigated the influence of Konjac Glucomannan (KGM) with varying degrees of polymerization (DKGMx) on the gelatinization and retrogradation characteristics of wheat starch, providing new insights into starch-polysaccharide interactions. This research uniquely focuses on the effects of DKGMx, utilizing multidisciplinary approaches including Rapid Visco Analysis (RVA), Differential Scanning Calorimetry (DSC), rheological testing, Low-Field Nuclear Magnetic Resonance (LF-NMR), and molecular simulations to assess the effects of DKGMx on gelatinization temperature, viscosity, structural changes post-retrogradation, and molecular interactions. Our findings revealed that higher degrees of polymerization (DP) of DKGMx significantly enhanced starch's pasting viscosity and stability, whereas lower DP reduced viscosity and interfered with retrogradation. High DP DKGMx promoted retrogradation by modifying moisture distribution. Molecular simulations revealed the interplay between low DP DKGMx and starch molecules. These interactions, characterized by increased hydrogen bonds and tighter binding to more starch chains, inhibited starch molecular rearrangement. Specifically, low DP DKGMx established a dense hydrogen bond network with starch, significantly restricting molecular mobility and rearrangement. This study provides new insights into the role of the DP of DKGMx in modulating wheat starch's properties, offering valuable implications for the functional improvement of starch-based foods and advancing starch science.


Subject(s)
Mannans , Polymerization , Starch , Triticum , Triticum/chemistry , Starch/chemistry , Viscosity , Mannans/chemistry , Hydrogen Bonding , Rheology , Molecular Dynamics Simulation , Calorimetry, Differential Scanning
2.
Org Lett ; 26(33): 7078-7082, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39119970

ABSTRACT

Multicomponent reactions hold the potential to maximize the synthetic efficiency in the preparation of diverse and complex molecular scaffolds. An unprecedented formal [3+1+1+1] annulation approach for the one-step synthesis of fluoroalkylated 2-H-pyrimidines commencing from perfluoroalkyl alkenes, paraformaldehyde, and ammonium carbonate is described. By harnessing readily accessible (CH2O)n and cheap (NH4)2CO3 as a formamidine surrogate, this method effectively replaces traditionally preformed amidines with a pyrimidine assembly. The multicomponent reaction proceeds in a step-economical, operationally simple, metal-free, and additive-free manner, featuring a broad substrate scope, excellent functional group compatibility, and scalability. The potential for the synthetic elaboration of the obtained 2-H-pyrimidine is further demonstrated in the alkylation and vinylation of its C2 position.

3.
Bioresour Technol ; 410: 131280, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39151565

ABSTRACT

Ethanol pre-fermentation of food waste effectively alleviates acidification; however, its effects on interspecies electron transfer remain unknown. This study configured the feed according to COD ratios of ethanol: sodium acetate: sodium propionate: sodium butyrate of 5:2:1.5:1.5 (ethanol-type anaerobic digestion) and 0:5:2.5:2.5 (control), and conducted semi-continuous anaerobic digestion (AD) experiments. The results showed that ethanol-type AD increased maximum tolerable organic loading rate (OLR) to 6.0 gCOD/L/d, and increased the methane production by 1.2-14.8 times compared to the control at OLRs of 1.0-5.0 gCOD/L/d. The abundance of the pilA gene, which was associated with direct interspecies electron transfer (DIET), increased by 5.6 times during ethanol-type AD. Hydrogenase genes related to interspecies hydrogen transfer (IHT), including hydA-B, hoxH-Y, hnd, ech, and ehb, were upregulated during ethanol-type AD. Ethanol-type AD improved methanogenic performance and enhanced microbial metabolism by stimulating DIET and IHT.


Subject(s)
Ethanol , Hydrogen , Methane , Methane/metabolism , Hydrogen/metabolism , Anaerobiosis , Ethanol/metabolism , Electron Transport , Bioreactors , Fermentation , Hydrogenase/metabolism
4.
Mol Med ; 30(1): 124, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138413

ABSTRACT

BACKGROUND: Obesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated. METHODS: In this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo. RESULTS: In hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3'UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling. CONCLUSIONS: Our study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes.


Subject(s)
Carrier Proteins , Insulin Resistance , Liver , PTEN Phosphohydrolase , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , RNA-Binding Proteins , Signal Transduction , Animals , Humans , Male , Mice , Carrier Proteins/metabolism , Carrier Proteins/genetics , Cytoskeletal Proteins/metabolism , Cytoskeletal Proteins/genetics , Diet, High-Fat/adverse effects , Hep G2 Cells , Liver/metabolism , Mice, Inbred C57BL , Palmitic Acid , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics
5.
Front Neurol ; 15: 1436238, 2024.
Article in English | MEDLINE | ID: mdl-39114534

ABSTRACT

Background: Hearing loss (HL) is the third most prevalent condition, significantly affecting individuals and society. Recent research has explored the potential impact of nutrition, particularly caffeine intake, on HL. While some studies focus on coffee, caffeine intake should be assessed across all dietary sources. This study examines the association between dietary caffeine intake and HL. Methods: Our cross-sectional study included 6,082 participants from the National Health and Nutrition Examination Survey (NHANES). Participants were divided into two groups based on their median caffeine intake: low and high. The study investigated two types of HL: speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL). Binary logistic regression analyzed the correlation between caffeine intake and HL, and a restricted cubic spline (RCS) model assessed potential non-linear associations. Subgroup analyses were also conducted. Results: High caffeine intake was associated with significantly higher rates of SFHL and HFHL compared to low intake (SFHL: 15.4% vs. 10%, HFHL: 30.5% vs. 20.6%, both p < 0.001). Unadjusted logistic regression showed a higher likelihood of SFHL (OR[95%CI] = 1.65[1.41-1.92]) and HFHL (OR[95%CI] = 1.69[1.50-1.90]) in high caffeine consumers. After adjusting for confounders, high caffeine intake remained significantly associated with SFHL (OR[95%CI] = 1.35[1.09-1.66]) but not HFHL (OR[95%CI] = 1.14[0.96-1.35]). The RCS model indicated a linear increase in the risk of SFHL and HFHL with higher caffeine intake (non-linear p = 0.229 for SFHL, p = 0.894 for HFHL). Subgroup analysis revealed that increased caffeine intake was linked to higher SFHL and HFHL risks in participants under 65 years but not in those 65 years and older (SFHL: p for interaction = 0.002; HFHL: p for interaction <0.001). Conclusion: Our study indicates a strong correlation between dietary caffeine intake and the risk of HL in American adults, particularly those under 65. High caffeine intake was linked to an increased risk of SFHL, but not HFHL, after adjusting for relevant variables.

6.
Obes Rev ; : e13818, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39191434

ABSTRACT

Interleukin-18 (IL-18), a potent and multifunctional pro-inflammatory cytokine, plays a critical role in regulating ß-cell failure, ß-cell death, insulin resistance, and various complications of diabetes mellitus (DM). It exerts its effects by triggering various signaling pathways, enhancing the production of pro-inflammatory cytokines and nitric oxide (NO), as well as promoting immune cells infiltration and ß-cells death. Abnormal alterations in IL-18 levels have been revealed to be strongly associated with the onset and development of DM and its complications. Targeting IL-18 may present a novel and promising approach for DM therapy. An increasing number of IL-18 inhibitors, including chemical and natural inhibitors, have been developed and have been shown to protect against DM and diabetic complications. This review provides a comprehensive understanding of the production, biological functions, action mode, and activated signaling pathways of IL-18. Next, we shed light on how IL-18 contributes to the pathogenesis of DM and its associated complications with links to its roles in the modulation of ß-cell failure and death, insulin resistance in various tissues, and pancreatitis. Furthermore, the therapeutic potential of targeting IL-18 for the diagnosis and treatment of DM is also highlighted. We hope that this review will help us better understand the functions of IL-18 in the pathogenesis of DM and its complications, providing novel strategies for DM diagnosis and treatment.

7.
Heliyon ; 10(13): e34193, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39071631

ABSTRACT

Objective and rationale: Hospital-acquired falls are common and serious adverse events in medical institutions, with high incidence and injury rates. Studying the occurrence patterns of hospital-acquired falls is important for preventing falls in hospitalized patients. However, the effect of meteorological factors on hospital-acquired falls has not been elucidated. Therefore, this study explored the impact of meteorological parameters on hospital-acquired falls in Chongqing, China, and provided new ideas for the clinical prevention of falls in patients. Methods: Correlation analysis and distributed lag nonlinear models were employed to analyze the relationship between 3890 cases of hospital-acquired falls and meteorological data in 13 hospitals in 11 districts and counties in Chongqing from January 2013 to April 2023. Results: The number of hospital-acquired falls demonstrated a nonlinear correlation with the daily average relative humidity and negatively correlated with sunshine duration; however, temperature, air pressure, and wind speed were not correlated. Compared to the reference humidity (87 %), the immediate effects of daily average relative humidity (65-68 % and 90-97 %) increased the risk of hospital-acquired falls on the same day (relative risk [RR]:1.027-1.243). When the daily average relative humidity was 95-97 %, lags of 0-1 d and 8-12 d had greater effects on falls (RR:1.073-1.243). The daily average relative humidities of 62-74 % and 91-97 % were statistically significant at cumulative relative risk (CRR)of 4, 7, 10, and 14 d with a cumulative lag (CRR: 1.111-4.277). On sex and age stratification, the lag and cumulative effects of relative humidity more significantly impacted falls in women and patients aged ≥65 years. Conclusion: Daily average relative humidity had a nonlinear correlation and lag effect on hospital-acquired falls; therefore, medical institutions should pay attention to the effect of relative humidity on hospital-acquired falls in patients, especially old and female patients.

8.
Org Lett ; 26(29): 6197-6202, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39004858

ABSTRACT

A silver-promoted three-component heterocyclization of alkynes, perfluoroalkyl halides, and 1,3-dinucleophiles was developed for the efficient synthesis of privileged (E)-perfluoroalkenyl pyrroles. The reaction proceeded through a rationally designed sequence of radical perfluoroalkylation and intramolecular defluorinative [3 + 2]-heterocyclization. The utility of perfluoroalkyl halide as a perfluoroalkenyl reagent, by selective and controllable functionalization of two inert C(sp3)-F bonds at vicinal carbon centers on the perfluoroalkyl chain, provides a new reaction mode for the synthesis of value-added organofluorides starting from the easily available and low-cost fluorinated feedstock.

9.
Food Chem ; 459: 140438, 2024 Nov 30.
Article in English | MEDLINE | ID: mdl-39024878

ABSTRACT

To investigate the structural characteristics of cell wall pectic polysaccharides from wampee, water soluble pectin (WSP), chelator-soluble pectin (CSP) and sodium carbonate-soluble pectin (SSP) were purified. And the inhibitory effects of wampee polyphenol (WPP) on pectinase when these cell wall pectic polysaccharides were used as substrates were also explored. Purified WSP (namely PWSP) had the lowest molecular weight (8.47 × 105 Da) and the highest GalA content (33.43%). While purified CSP (called PCSP) and SSP contained more abundant rhamnogalacturonan I side chains. All of them were low-methoxy pectin (DE < 50%). Enzyme activity and kinetics analysis showed that the inhibition of pectinase by wampee polyphenol was reversible and mixed type. When SSP was used as the substrate, WPP had the strongest inhibition (IC50 = 1.96 ± 0.06 mg/mL) on pectinase. Fluorescence quenching results indicated that WPP inhibited enzyme activity by interacting with substrates and enzymes. Therefore, WPP has the application potential in controlling softening of fruits and vegetables.


Subject(s)
Cell Wall , Pectins , Polygalacturonase , Polyphenols , Polygalacturonase/chemistry , Polygalacturonase/metabolism , Pectins/chemistry , Cell Wall/chemistry , Cell Wall/metabolism , Polyphenols/chemistry , Polyphenols/pharmacology , Kinetics , Molecular Weight , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Polysaccharides/chemistry , Polysaccharides/metabolism , Polysaccharides/pharmacology , Fruit/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology
10.
RSC Adv ; 14(25): 17557-17570, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38828277

ABSTRACT

With ceritinib as the lead, a series of novel compounds containing the sulfoxide structure were synthesized and evaluated as anaplastic lymphoma kinase inhibitors. Among them, compounds 18a-d exhibited excellent anti-proliferation activities on H2228 EML4-ALK cancer cell lines with 14-28 nM of the IC50 values. In xenograft mouse models, 18a-d inhibited tumor growth with an excellent inhibitory rate of 75.0% to 86.0% at the dosage of 20 mg kg-1 as compared to 72.0% of the reference ceritinib. Using 18d as a representative, which exhibited the best in vivo results, we carried out mechanistic studies such as anti-colony formation, induced tumor cell apoptosis, ALK kinase protein phosphorylation in H2228 tumor cells, and molecular docking. All these results indicate that compound 18d is a good anti-tumor lead compound and worthy of further study.

11.
Front Immunol ; 15: 1396260, 2024.
Article in English | MEDLINE | ID: mdl-38863712

ABSTRACT

Background: Encephalitozoon hellem (E. hellem) infection is a zoonotic disease, rarely observed in individuals, causing various clinical manifestations including diarrhea, keratoconjunctivitis, cystitis, etc. E. hellem infection after hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication. Case presentation: Herein, we present a case of E. hellem infection developing during HLA-haploidentical HSCT in a 9-year-old boy who suffered from aplastic anemia. On 15 days after HSCT, the patient developed recurrent and prolonged fever, diarrhea and hematuria. It is challenging to differentiate whether the symptoms mentioned in this case are caused by graft-versus-host disease (GVHD) or a specific infection. Based on the result of metagenomic next-generation sequencing (mNGS) and clinical observation, the patient was diagnosed as E. hellem infection, and received albendazole and decreased the immunosuppressive treatment. Finally, he had recovered. Conclusion: We should pay attention to the uncommon disease caused by the E. hellem infection after HSCT, especially in cases with immune reconstitution unrecovered. Among those rare infection, mNGS can be performed for better understanding the source of infection and targeted therapy, which can benefit the patients.


Subject(s)
Hematopoietic Stem Cell Transplantation , Transplantation, Haploidentical , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Child , Transplantation, Haploidentical/adverse effects , Anemia, Aplastic/therapy , Albendazole/therapeutic use , Graft vs Host Disease/etiology , Transplantation, Homologous/adverse effects
12.
Genes (Basel) ; 15(6)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38927679

ABSTRACT

Hypoxia is a globally pressing environmental problem in aquatic ecosystems. In the present study, a comprehensive analysis was performed to evaluate the effects of hypoxia on physiological responses (hematology, cortisol, biochemistry, hif gene expression and the HIF pathway) of hybrid sturgeons (Acipenser schrenckii ♂ × Acipenser baerii ♀). A total of 180 hybrid sturgeon adults were exposed to dissolved oxygen (DO) levels of 7.00 ± 0.2 mg/L (control, N), 3.5 ± 0.2 mg/L (moderate hypoxia, MH) or 1.00 ± 0.1 mg/L (severe hypoxia, SH) and were sampled at 1 h, 6 h and 24 h after hypoxia. The results showed that the red blood cell (RBC) counts and the hemoglobin (HGB) concentration were significantly increased 6 h and 24 h after hypoxia in the SH group. The serum cortisol concentrations gradually increased with the decrease in the DO levels. Moreover, several serum biochemical parameters (AST, AKP, HBDB, LDH, GLU, TP and T-Bil) were significantly altered at 24 h in the SH group. The HIFs are transcription activators that function as master regulators in hypoxia. In this study, a complete set of six hif genes were identified and characterized in hybrid sturgeon for the first time. After hypoxia, five out of six sturgeon hif genes were significantly differentially expressed in gills, especially hif-1α and hif-3α, with more than 20-fold changes, suggesting their important roles in adaptation to hypoxia in hybrid sturgeon. A meta-analysis indicated that the HIF pathway, a major pathway for adaptation to hypoxic environments, was activated in the liver of the hybrid sturgeon 24 h after the hypoxia challenge. Our study demonstrated that hypoxia, particularly severe hypoxia (1.00 ± 0.1 mg/L), could cause considerable stress for the hybrid sturgeon. These results shed light on their adaptive mechanisms and potential biomarkers for hypoxia tolerance, aiding in aquaculture and conservation efforts.


Subject(s)
Fishes , Animals , Fishes/genetics , Fishes/metabolism , Hypoxia/genetics , Hypoxia/metabolism , Hydrocortisone/blood , Oxygen/metabolism , Fish Proteins/genetics , Fish Proteins/metabolism , Gene Expression Regulation , Hemoglobins/metabolism , Hemoglobins/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1/metabolism , Hypoxia-Inducible Factor 1/genetics
13.
Cell Commun Signal ; 22(1): 345, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943195

ABSTRACT

BACKGROUND: The neonatal mammalian heart exhibits considerable regenerative potential following injury through cardiomyocyte proliferation, whereas mature cardiomyocytes withdraw from the cell cycle and lose regenerative capacities. Therefore, investigating the mechanisms underlying neonatal cardiomyocyte proliferation and regeneration is crucial for unlocking the regenerative potential of adult mammalian heart to repair damage and restore contractile function following myocardial injury. METHODS: The Tudor staphylococcal nuclease (Tudor-SN) transgenic (TG) or cardiomyocyte-specific knockout mice (Myh6-Tudor-SN -/-) were generated to investigate the role of Tudor-SN in cardiomyocyte proliferation and heart regeneration following apical resection (AR) surgery. Primary cardiomyocytes isolated from neonatal mice were used to assess the influence of Tudor-SN on cardiomyocyte proliferation in vitro. Affinity purification and mass spectrometry were employed to elucidate the underlying mechanism. H9c2 cells and mouse myocardia with either overexpression or knockout of Tudor-SN were utilized to assess its impact on the phosphorylation of Yes-associated protein (YAP), both in vitro and in vivo. RESULTS: We previously identified Tudor-SN as a cell cycle regulator that is highly expressed in neonatal mice myocardia but downregulated in adults. Our present study demonstrates that sustained expression of Tudor-SN promotes and prolongs the proliferation of neonatal cardiomyocytes, improves cardiac function, and enhances the ability to repair the left ventricular apex resection in neonatal mice. Consistently, cardiomyocyte-specific knockout of Tudor-SN impairs cardiac function and retards recovery after injury. Tudor-SN associates with YAP, which plays important roles in heart development and regeneration, inhibiting phosphorylation at Ser 127 and Ser 397 residues by preventing the association between Large Tumor Suppressor 1 (LATS1) and YAP, correspondingly maintaining stability and promoting nuclear translocation of YAP to enhance the proliferation-related genes transcription. CONCLUSION: Tudor-SN regulates the phosphorylation of YAP, consequently enhancing and prolonging neonatal cardiomyocyte proliferation under physiological conditions and promoting neonatal heart regeneration after injury.


Subject(s)
Adaptor Proteins, Signal Transducing , Animals, Newborn , Cell Proliferation , Myocytes, Cardiac , Regeneration , YAP-Signaling Proteins , Animals , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/physiology , Myocytes, Cardiac/cytology , Phosphorylation , YAP-Signaling Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Mice , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Heart/physiology , Mice, Knockout , Rats
14.
Eur J Med Chem ; 275: 116590, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38908104

ABSTRACT

The C797S mutation of EGFR leads to Osimertinib resistance by blocking the covalent binding of Cys797. To develop new agents that can overcome EGFR mutation resistance, thirty seven new cyclopropane sulfonamide derivatives were synthesized and evaluated as EGFRL858R/T790M/C797S or EGFRDel19/T790M/C797S inhibitors by structure-based screening. Most of the synthesized compounds exhibit good to excellent anti proliferation activity against to BaF3-EGFR L858R/T790M/C797S and BaF3-C797S/Del19/T790M cancer cell lines. Representative compounds 8l showed inhibitory activity against the two cancer cell lines with the IC50 values of 0.0012 and 0.0013 µM, respectively. Another compound 8h, exhibited slightly lower activity (0.0042 and 0.0034 µM of the IC50 values) to both of the two tri-mutation cell lines, but excellent activities against H1975 and PC9 cells with IC50 values of 13 and 19 nM, respectively. Considering the acquired drug resistance of tumors is a gradual process, we chose 8h for further in vivo and mechanism study. 8h was demonstrated significantly inhibited tumor growth with 72.1 % of the TGI in the BaF3/EGFR-TM xenograft tumor model and 83.5 % in the H1975-DM xenograft tumor model. Compound 8h was confirmed to be safe with no significant side effects as showed by the results of in vitro assay of human normal cells and the sections of animals major organs. Mechanism studies showed that in addition to inhibiting EGFR mutations, 8h can also target the tumor microenvironment and induce tumor cell apoptosis. All these results indicate that 8h deserves further investigation as an EGFR inhibitor to overcome C797S-mediated resistance.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Cyclopropanes , Drug Resistance, Neoplasm , ErbB Receptors , Mutation , Protein Kinase Inhibitors , Sulfonamides , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/metabolism , Humans , Sulfonamides/pharmacology , Sulfonamides/chemistry , Sulfonamides/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Animals , Drug Resistance, Neoplasm/drug effects , Structure-Activity Relationship , Cell Proliferation/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Cyclopropanes/pharmacology , Cyclopropanes/chemistry , Cyclopropanes/chemical synthesis , Mice , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Molecular Structure , Drug Discovery , Cell Line, Tumor , Mice, Nude
15.
Int J Biol Macromol ; 273(Pt 1): 133002, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38851613

ABSTRACT

Here, a polysaccharide derivative acryloyl chitosan (AcCS) is exploited as macro-crosslinker to synthesize a novel ionogel poly (acrylic acid-co-1-Vinyl-3-butyl imidazolium chloride) (AA-IL/AcCS) via a one-pot method. AcCS provides abundant physical and chemical crosslinking sites contributing to the high mechanical stretchability (elongation at break 600 %) and strength (tensile strength 137 kPa) of AA-IL/AcCS. The high-density of dynamic bonds (hydrogen bonds and electrostatic interactions) in the network of ionogels enables self-healing and self-adhesive features of AA-IL/AcCS. Meanwhile, AA-IL/AcCS exhibits high ionic conductivity (0.1 mS/cm) at room temperature and excellent antifreeze ability (-58 °C). The AA-IL/AcCS-based sensor shows diverse sensory capabilities towards temperature and humidity, moreover, it could precisely detect human motions and handwritings signals. Furthermore, AA-IL/AcCS exhibits excellent bactericidal properties against both gram-positive and gram-negative bacteria. This work opens the possibility of polysaccharides as a macro-crosslinkers for preparing ionogel-based sensors for wearable electronics.


Subject(s)
Chitosan , Freezing , Chitosan/chemistry , Cross-Linking Reagents/chemistry , Gels/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Electric Conductivity , Adhesives/chemistry , Humans , Wearable Electronic Devices , Tensile Strength
16.
Cancer Lett ; 592: 216934, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38710299

ABSTRACT

The Staphylococcal nuclease and Tudor domain containing 1 (SND1) has been identified as an oncoprotein. Our previous study demonstrated that SND1 impedes the major histocompatibility complex class I (MHC-I) assembly by hijacking the nascent heavy chain of MHC-I to endoplasmic reticulum-associated degradation. Herein, we aimed to identify inhibitors to block SND1-MHC-I binding, to facilitate the MHC-I presentation and tumor immunotherapy. Our findings validated the importance of the K490-containing sites in SND1-MHC-I complex. Through structure-based virtual screening and docking analysis, (-)-Epigallocatechin (EGC) exhibited the highest docking score to prevent the binding of MHC-I to SND1 by altering the spatial conformation of SND1. Additionally, EGC treatment resulted in increased expression levels of membrane-presented MHC-I in tumor cells. The C57BL/6J murine orthotopic melanoma model validated that EGC increases infiltration and activity of CD8+ T cells in both the tumor and spleen. Furthermore, the combination of EGC with programmed death-1 (PD-1) antibody demonstrated a superior antitumor effect. In summary, we identified EGC as a novel inhibitor of SND1-MHC-I interaction, prompting MHC-I presentation to improve CD8+ T cell response within the tumor microenvironment. This discovery presents a promising immunotherapeutic candidate for tumors.


Subject(s)
Antigen Presentation , CD8-Positive T-Lymphocytes , Catechin , Endonucleases , Mice, Inbred C57BL , Animals , CD8-Positive T-Lymphocytes/immunology , Mice , Humans , Antigen Presentation/immunology , Endonucleases/metabolism , Catechin/analogs & derivatives , Catechin/pharmacology , Cell Line, Tumor , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class I/metabolism , Molecular Docking Simulation , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Melanoma, Experimental/metabolism , Melanoma, Experimental/therapy , Antigens, Neoplasm/immunology , Antigens, Neoplasm/metabolism
17.
Int J Biol Macromol ; 271(Pt 2): 132473, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38795886

ABSTRACT

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) serve as transcriptional co-activators that dynamically shuttle between the cytoplasm and nucleus, resulting in either the suppression or enhancement of their downstream gene expression. Recent emerging evidence demonstrates that YAP/TAZ is strongly implicated in the pathophysiological processes that contribute to cardiovascular diseases (CVDs). In the cardiovascular system, YAP/TAZ is involved in the orchestration of a range of biological processes such as oxidative stress, inflammation, proliferation, and autophagy. Furthermore, YAP/TAZ has been revealed to be closely associated with the initiation and development of various cardiovascular diseases, including atherosclerosis, pulmonary hypertension, myocardial fibrosis, cardiac hypertrophy, and cardiomyopathy. In this review, we delve into recent studies surrounding YAP and TAZ, along with delineating their roles in contributing to the pathogenesis of CVDs with a link to various physiological processes in the cardiovascular system. Additionally, we highlight the current potential drugs targeting YAP/TAZ for CVDs therapy and discuss their challenges for translational application. Overall, this review may offer novel insights for understanding and treating cardiovascular disorders.


Subject(s)
Cardiovascular Diseases , Signal Transduction , YAP-Signaling Proteins , Humans , Cardiovascular Diseases/metabolism , YAP-Signaling Proteins/metabolism , Animals , Transcription Factors/metabolism , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Adaptor Proteins, Signal Transducing/metabolism
18.
Chem Asian J ; 19(14): e202400181, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38705859

ABSTRACT

In Li-ion batteries, the origin of memory effect in Al-doped Li4Ti5O12 has been revealed as the reversible Al-ion switching between 8a and 16c sites in the spinel structure, but it is still not clear about that for olivine LiFePO4, which is one of the most important cathode materials. In this work, a series of Na-doped and Ti-doped LiFePO4 are prepared in a high-temperature solid-state method, electrochemically investigated in Li-ion batteries and characterized by X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Magic-Angle-Spinning Nuclear Magnetic Resonance (MAS NMR). Compared with non-doped LiFePO4, the Ti doping can simultaneously suppress the memory effect and the Li-Fe anti-site, while they are simultaneously enhanced by the Na doping. Meanwhile, the Ti doping improves the electrochemical performance of LiFePO4, opposite to the Na doping. Accordingly, a schematic diagram of phase transition is proposed to interpret the memory effect of LiFePO4, in which the memory effect is attributed to the defect of Li-Fe anti-site.

19.
Org Biomol Chem ; 22(14): 2797-2812, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38506310

ABSTRACT

An effective [3 + 2] cycloaddition reaction of difluoromethyl or trifluoromethyl hydrazonoyl bromides with alkylidene pyrazolones was disclosed. This method provides an efficient approach for accessing a variety of highly functionalized fluoroalkyl spiropyrazolones in good yields. This protocol also features some advantages such as easily available and stable substrates, simple operation procedures, and atom and step economy. The formation of (cis)- and (trans)-products was discussed.

20.
Food Chem X ; 22: 101253, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38444553

ABSTRACT

This study investigated the regulation effect of magnetic field combined with low temperature storage on postharvest quality and cell wall pectic-polysaccharide degradation of wampee stored for 15 d at 4 °C and 15 °C. Results showed that magnetic field combined with low temperature storage reduced browning rate of fruit after 15 d storage, but its effect on weight loss rate and total soluble solids (TSS) did not surpass that of storage temperature. Interestingly, contents of flavonoid, total phenols and malondialdehyde (MDA) were also lowered at varying degrees by combined treatment. Furthermore, molecular weight distribution and monosaccharide compositions of cell wall pectic-polysaccharides were also affected, which resulted from the coordinated action of cell wall pectin-degrading enzymes. The activities of these enzymes during storage, including polygalacturonase (PG), pectin methylesterase (PME) and ß-galactosidase (ß-Gal) in treated wampee decreased. These findings suggested that magnetic field combined with low temperature storage was an effective technology and had great potential in preservation of postharvest wampee in future.

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