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1.
Nat Commun ; 15(1): 3892, 2024 May 08.
Article En | MEDLINE | ID: mdl-38719816

As a sustainable alternative to fossil fuel-based manufacture of bulk oxygenates, electrochemical synthesis using CO and H2O as raw materials at ambient conditions offers immense appeal. However, the upscaling of the electrosynthesis of oxygenates encounters kinetic bottlenecks arising from the competing hydrogen evolution reaction with the selective production of ethylene. Herein, a catalytic relay system that can perform in tandem CO capture, activation, intermediate transfer and enrichment on a Cu-Ag composite catalyst is used for attaining high yield CO-to-oxygenates electrosynthesis at high current densities. The composite catalyst Cu/30Ag (molar ratio of Cu to Ag is 7:3) enables high efficiency CO-to-oxygenates conversion, attaining a maximum partial current density for oxygenates of 800 mA cm-2 at an applied current density of 1200 mA cm-2, and with 67 % selectivity. The ability to finely control the production of ethylene and oxygenates highlights the principle of efficient catalyst design based on the relay mechanism.

2.
J Nanobiotechnology ; 22(1): 168, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38610015

BACKGROUND: Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. RESULTS: The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. CONCLUSIONS: Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.


Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Animals , Mice , Carcinoma, Squamous Cell/drug therapy , Squamous Cell Carcinoma of Head and Neck , Mouth Neoplasms/drug therapy , Tissue Distribution , Macrophages , Doxorubicin/pharmacology , Hydrogen-Ion Concentration , Tumor Microenvironment
3.
BMC Psychiatry ; 24(1): 210, 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38500067

BACKGROUND: Current research has been focusing on non-suicidal self-injury (NSSI) behaviors among adolescents with depression. Although family intimacy and adaptability are considered protective factors for NSSI, evidence supporting this relationship is lacking. OBJECTIVE: This study aims to examine the mechanisms operating in the relationship between family intimacy and adaptability and NSSI behaviors among adolescents. METHODS: A self-administered general demographic information questionnaire, the Behavioral Functional Assessment Scale for Non-Suicidal Self-Injury, the Family Intimacy and Adaptability Scale, the Connor-Davidson Resilience Scale, and the Self-Assessment of Depression Scale were distributed among adolescents with depression in three tertiary hospitals in Jiangsu Province. RESULTS: The relationship between family intimacy and adaptability and NSSI was assessed among 596 adolescents with depression. The results revealed the following: (1) Family intimacy and adaptability were negatively correlated with NSSI behavior. (2) Psychological resilience and depression levels acted as chain mediators in the relationship between family intimacy and adaptability and NSSI behavior. CONCLUSIONS: Enhancing psychological resilience, controlling depressive symptoms, and reducing depression severity among adolescents by improving their family intimacy and adaptability are conducive to preventing and mitigating their NSSI behaviors.


Resilience, Psychological , Self-Injurious Behavior , Adolescent , Humans , Mediation Analysis , Self-Injurious Behavior/psychology , Psychological Tests
4.
J Colloid Interface Sci ; 665: 204-218, 2024 Jul.
Article En | MEDLINE | ID: mdl-38522160

Upcycle polyethylene terephthalate (PET) waste by photoreforming (PR) is a sustainable and green approach to tackle environmental problems but with challenges to obtain valuable oxidation products and high purity hydrogen simultaneously. Noble metal cocatalysts are essential to enhance the overall PR reaction efficacy. In this work, TiO2 nanotubes (TiO2 NTs) decorated with single Pt atoms (Pt1/TiO2) or Pt nanoparticles (PtNPs/TiO2) are used in the photoreforming reaction (in one batch), and the oxidation products from ethylene glycol (EG, hydrolysed product of PET) in liquid phase and hydrogen are detected. With Pt1/TiO2, EG is oxidized to glyoxal, glyoxylate or lactate, and hydrogen evolution rate (r H2) reaches 51.8 µmol⋅h-1⋅gcat-1, that is 30 times higher than that of TiO2. For PtNPs/TiO2 (size of Pt NPs: 1.97 nm), hydrogen evolution reaches 219.1 µmol⋅h-1⋅gcat-1, but with the oxidation product of acetate only. DFT calculation demonstrates that for Pt NPs, the reaction path for hydrogen evolution is preferred thermodynamically, due to the formation of Schottky junction. On the oxidation of EG, theoretical and spectroscopic analysis suggest that bidentate adsorption of EG at the interface is facile on Pt1/TiO2, compared to that on PtNPs/TiO2 (two Pt sites), but oxidation products, adsorb less strongly, compared to PtNPs/TiO2, that eventually regulates the distribution of oxidation products. The results thus demonstrate the bifunctions of Pt in the PR reaction, i.e., electron transfer mediator for hydrogen evolution and reactive sites for molecules adsorption. The oxidation reaction is dominated by the adsorption-desorption behavior of molecules but the reduction reaction is controlled by the electron transfer. In addition, acidification of pretreated PET alkaline solution achieves separation of pure terephthalic acid (PTA), which further improves the reaction efficiency possibly by offering high density of active sites and acidic environment. Our work thus demonstrates that to upcycle PET plastics, an optimized process can be reached by atomic design of photocatalysts and proper treatment on the plastic wastes.

5.
Angew Chem Int Ed Engl ; 63(14): e202317167, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38323917

Hydroxylamine (NH2OH) is an important feedstock in fuels, pharmaceuticals, and agrochemicals. Nanostructured electrocatalysts drive green electrosynthesis of hydroxylamine from nitrogen oxide species in water. However, current electrocatalysts still suffer from low selectivity and manpower-consuming trial-and-error modes, leaving unclear selectivity/activity origins and a lack of catalyst design principles. Herein, we theoretically analyze key determinants of selectivity/activity and propose the adsorption energy of NHO (Gad(*NHO)) as a performance descriptor. A weak *NH2OH binding affinity and a favorable reaction pathway (*NHO pathway) jointly enable single-atom catalysts (SACs) with superior NH2OH selectivity. Then, an activity volcano plot of Gad(*NHO) is established to predict a series of SACs and discover Mn SACs as optimal electrocatalysts that exhibit pH-dependent activity. These theoretical prediction results are also confirmed by experimental results, rationalizing our Gad(*NHO) descriptor. Furthermore, Mn-Co geminal-atom catalysts (GACs) are predicted to optimize Gad(*NHO) and are experimentally proved to enhance NH2OH formation.

6.
Tissue Eng Regen Med ; 21(2): 291-308, 2024 02.
Article En | MEDLINE | ID: mdl-37903982

BACKGROUND: The addition of growth factiors is commonly applied to improve the osteogenic differentiation of stem cells. However, for human pluripotent stem cells (hPSCs), their complex differentiation processes result in the unknown effect at different stages. In this study, we focused on the widely used bone forming peptide-1 (BFP-1) and investigated the effect and mechanisms of its addition on the osteogenic induction of hPSCs as a function of the supplementation period. METHODS: Monolayer-cultured hPSCs were cultured in osteogenic induction medium for 28 days, and the effect of BFP-1 peptide addition at varying weeks was examined. After differentiation for varying days (0, 7, 14, 21 and 28), the differentiation efficiency was determined by RT-PCR, flow cytometry, immunofluorescence, and alizarin red staining assays. Moreover, the expression of marker genes related to germ layers and epithelial-mesenchymal transition (EMT) was investigated at day 7. RESULTS: Peptide treatment during the first week promoted the generation of mesoderm cells and mesenchymal-like cells from hiPSCs. Then, the upregulated expression of osteogenesis marker genes/proteins was detected in both hESCs and hiPSCs during subsequent inductions with BFP-1 peptide treatment. Fortunately, further experimental design confirmed that treating the BFP-1 peptide during 7-21 days showed even better performance for hESCs but was ineffective for hiPSCs. CONCLUSION: The differentiation efficiency of cells could be improved by determining the optimal treatment period. Our study has great value in maximizing the differentiation of hPSCs by adding osteogenesis peptides based on the revealed mechanisms and promoting the application of hPSCs in bone tissue regeneration.


Mesenchymal Stem Cells , Pluripotent Stem Cells , Humans , Osteogenesis , Mesenchymal Stem Cells/metabolism , Cell Differentiation , Peptides/pharmacology , Peptides/metabolism
7.
J Control Release ; 366: 28-43, 2024 02.
Article En | MEDLINE | ID: mdl-38151121

Given the inherent complexity of cancer treatment and the limitations of singular therapeutic modalities, the development of an optimal nanocarrier system capable of facilitating synergistic organic therapy remains a profound challenge. Herein, a synergetic chemo/photothermal therapy nanoplatform was exploited to specifically tailor for the augmented treatment of oral cancer. A cancer cell membrane-camouflaged nanocarrier was developed with a polymeric core encapsulating doxorubicin (DOX). The designed nanoparticles (CC@DOXNPs) inherited the functional membrane proteins from the source cancer cells, endowing their remarkable ability to selectively target cancer cells delivery both in vitro and in vivo. Moreover, indocyanine green (ICG), modified with the phospholipid polymer DSPE-PEG2000, was introduced into the cancer cell membrane to enable photothermal therapy. Remarkably, as evaluated in a preclinical subcutaneous and orthotopic mice model of oral cancer, biomimetic composite nanotherapeutics (lip-CC@DOXNPs) could significantly accumulate into tumor lesion and effectively suppress tumor growth under the near-infrared (NIR, 808 nm) irradiation, without causing the undesirable systematic toxicity. Moreover, RNA sequence analyses indicated that chemo/photothermal therapy triggers the intrinsic mitochondria-mediated apoptosis through the p53 signaling pathway. Combined with gene expression results, this intrinsic mitochondria-mediated apoptosis pathway was further demonstrated. Collectively, this multifaceted nanoplatforms possess a remarkable capability for tumor-targeting drug delivery, and the proficient photothermal conversion ability, rendering them an ideal therapeutic approach for oral cancer treatment.


Hyperthermia, Induced , Mouth Neoplasms , Mice , Animals , Phototherapy/methods , Biomimetics , Hyperthermia, Induced/methods , Drug Delivery Systems/methods , Mouth Neoplasms/drug therapy
8.
Redox Biol ; 67: 102900, 2023 11.
Article En | MEDLINE | ID: mdl-37748319

Bone marrow-derived mesenchymal stem cells (BMMSCs) derived from myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients often show a shift in the balance between osteoblastogenesis and adipogenesis. It was suggested that BMMSCs can potentially undergo reprogramming or educational processes. However, the results of reprogrammed differentiation have been inconclusive. In this study, clinical samples, co-culture models and mouse models were employed to explore the association of MDS/AML clonal cells and BMMSCs differentiation. We found that clonal MDS/AML cells promoted adipogenic differentiation and inhibited osteogenic differentiation of BMMSCs, which in turn promoted MDS expansion. Mass spectrometry and cytokine array were used to identify the molecules to drive the BMMSCs differentiation in MDS/AML. Mechanistically, highly expressed transcription factor TWIST1 in clonal MDS/AML cells induces MDS/AML cells to secrete more IFN-γ, which can induce oxidative stress through STAT1-dependent manner, ultimately causing enhanced adipogenic differentiation and inhibited osteogenic differentiation in BMMSCs. Overall, our findings suggest that targeting the driving oncogenes in malignant clonal cells, such as TWIST1, may offer new therapeutic strategies by remodeling the surrounding bone marrow microenvironment in the treatment of MDS/AML and other hematopoietic malignancies.


Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Animals , Humans , Mice , Adipogenesis/genetics , Bone Marrow/metabolism , Cell Differentiation/genetics , Leukemia, Myeloid, Acute/metabolism , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/metabolism , Myelodysplastic Syndromes/pathology , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Osteogenesis/genetics , Tumor Microenvironment , Twist-Related Protein 1/genetics , Twist-Related Protein 1/metabolism
9.
Cell Commun Signal ; 21(1): 255, 2023 09 22.
Article En | MEDLINE | ID: mdl-37736724

Chemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistance in MDS/AML. However, the underlying mechanism of TWIST1 dysregulation in DAC resistance remained enigmatic. Here, we found that O-GlcNAc modification was upregulated in CD34+ cells from MDS/AML patients who do not respond to DAC treatment. Functional study revealed that O-GlcNAcylation could stabilize TWIST1 by impeding its interaction with ubiquitin E3 ligase CBLC. In addition, as one typical transcription factor, TWIST1 could bind to the promoter of O-GlcNAc transferase (OGT) gene and activate its transcription. Collectively, we highlighted the crucial role of the O-GlcNAcylated TWIST1 in the chemoresistance capacity of MDS/AML clonal cells, which may pave the way for the development of a new therapeutic strategy targeting O-GlcNAcylated proteins and reducing the ratio of MDS/AML relapse. Video Abstract.


Myelodysplastic Syndromes , Oncogenes , Humans , Decitabine/pharmacology , N-Acetylglucosaminyltransferases , Myelodysplastic Syndromes/drug therapy , Nuclear Proteins , Twist-Related Protein 1
10.
J Nanobiotechnology ; 21(1): 307, 2023 Aug 29.
Article En | MEDLINE | ID: mdl-37644442

A disorder of cholesterol homeostasis is one of the main initiating factors in the progression of atherosclerosis (AS). Metabolism and removal of excess cholesterol facilitates the prevention of foam cell formation. However, the failure of treatment with drugs (e.g. methotrexate, MTX) to effectively regulate progression of disease may be related to the limited drug bioavailability and rapid clearance by immune system. Thus, based on the inflammatory lesion "recruitment" properties of macrophages, MTX nanoparticles (MTX NPs) camouflaged with macrophage membranes (MM@MTX NPs) were constructed for the target to AS plaques. MM@MTX NPs exhibited a uniform hydrodynamic size around ~ 360 nm and controlled drug release properties (~ 72% at 12 h). After the macrophage membranes (MM) functionalized "homing" target delivery to AS plaques, MM@MTX NPs improved the solubility of cholesterol by the functionalized ß-cyclodextrin (ß-CD) component and significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1, resulting in efficiently inhibiting the formation of foam cells. Furthermore, MM@MTX NPs could significantly reduce the area of plaque, aortic plaque and cholesterol crystals deposition in ApoE-/- mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS.


Atherosclerosis , Plaque, Atherosclerotic , Animals , Mice , Foam Cells , Biomimetics , Atherosclerosis/drug therapy , Biological Transport
11.
Nat Commun ; 14(1): 4289, 2023 Jul 18.
Article En | MEDLINE | ID: mdl-37463898

Conductive hydrogels require tunable mechanical properties, high conductivity and complicated 3D structures for advanced functionality in (bio)applications. Here, we report a straightforward strategy to construct 3D conductive hydrogels by programable printing of aqueous inks rich in poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) inside of oil. In this liquid-in-liquid printing method, assemblies of PEDOT:PSS colloidal particles originating from the aqueous phase and polydimethylsiloxane surfactants from the other form an elastic film at the liquid-liquid interface, allowing trapping of the hydrogel precursor inks in the designed 3D nonequilibrium shapes for subsequent gelation and/or chemical cross-linking. Conductivities up to 301 S m-1 are achieved for a low PEDOT:PSS content of 9 mg mL-1 in two interpenetrating hydrogel networks. The effortless printability enables us to tune the hydrogels' components and mechanical properties, thus facilitating the use of these conductive hydrogels as electromicrofluidic devices and to customize near-field communication (NFC) implantable biochips in the future.

12.
PLoS One ; 18(6): e0283303, 2023.
Article En | MEDLINE | ID: mdl-37352305

Two different drying methods (vacuum freeze-drying and hot-air drying) were used to dry mulberry of three varieties 'Baiyuwang'(D1), 'Longsang'(D2) and 'Zhongshen.1'(D3), and the fresh fruit of each variety was used as the control. The effects of different processing conditions on the physical characteristics, nutrients, functional components and antioxidant activity of mulberry fruit were analyzed. The results show that after different drying methods, after vacuum freeze-drying, the physical properties of dried mulberry fruit such as wettability, hygroscopic property and water retention, soluble protein, ascorbic acid and other nutrients, functional components such as polyphenols, resveratrol, chlorogenic acid and anthocyanin, and antioxidant activities such as DPPH free radical scavenging ability and ABTS free radical scavenging ability were superior to hot air drying (P < 0.01). It was concluded that vacuum freeze drying was more beneficial for retaining the original quality of mulberry than hot air drying. This study can provide a retaining theoretical basis for mulberry deep processing and comprehensive development and utilization.


Fruit , Morus , Fruit/chemistry , Morus/chemistry , Vacuum , Antioxidants/chemistry , Freeze Drying , Free Radicals , Desiccation/methods
13.
Biochim Biophys Acta Mol Cell Res ; 1870(6): 119492, 2023 08.
Article En | MEDLINE | ID: mdl-37207914

Chemotherapeutic drugs are used routinely for treatment for myelodysplastic syndrome (MDS) patients but are ineffective in a substantial proportion of patients. Abnormal hematopoietic microenvironments, in addition to spontaneous characteristics of malignant clones, contribute to ineffective hematopoiesis. In our study, we found expression of enzyme ß1,4-galactosyltransferase 1 (ß4GalT1), which regulates N-acetyllactosamine (LacNAc) modification of proteins, is elevated in bone marrow stromal cells (BMSCs) of MDS patients, and also contributes to drug ineffectiveness through a protective effect on malignant cells. Our investigation of the underlying molecular mechanism revealed that ß4GalT1-overexpressing BMSCs promoted MDS clone cells resistant to chemotherapeutic drugs and also showed enhanced secretion of cytokine CXCL1 through degradation of tumor protein p53. Chemotherapeutic drug tolerance of myeloid cells was inhibited by application of exogenous LacNAc disaccharide and blocking of CXCL1. Our findings clarify the functional role of ß4GalT1-catalyzed LacNAc modification in BMSCs of MDS. Clinical alteration of this process is a potential new strategy that may substantially enhance effectiveness of therapies for MDS and other malignancies, by targeting a niche interaction.


Mesenchymal Stem Cells , Myelodysplastic Syndromes , Humans , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/metabolism , Mesenchymal Stem Cells/metabolism , Hematopoietic Stem Cells/metabolism , Bone Marrow Cells/metabolism , Hematopoiesis
14.
Front Pharmacol ; 14: 1158945, 2023.
Article En | MEDLINE | ID: mdl-37033644

Inflammatory bowel disease (IBD) is a chronic recurrent intestinal disease. The incidence rate of IBD is increasing year by year, which seriously endangers human health worldwide. More and more studies have shown that medicinal plants or their main phytochemicals have great potential in the treatment of intestinal diseases. However, the disadvantages of low oral absorption rate, low biological distribution and low systemic bioavailability limit their clinical application to a certain extent. In recent years, the application of nanotechnology has made it possible to treat IBD. Nanoparticles (NPs) drug delivery system has attracted special attention in the treatment of IBD due to its small size, low immunogenicity, surface modification diversity, targeting and other advantages. Synthetic nanoparticles and extracellular vehicles (EVs) can deliver drug components to colon, and play a role in anti-inflammation, regulation of oxidative stress, improvement of intestinal flora, etc. In addition, some medicinal plants can secrete EVs by themselves, and carry biological molecules with therapeutic effects to act on the intestine. Some clinical trials to evaluate the safety, tolerance, toxicity and effectiveness of EVs-loaded drugs in IBD are also progressing steadily. This review introduces that synthetic nanoparticles and medicinal plants derived EVs can play an important role in the treatment of IBD by carrying the effective active phytochemicals of medicinal plants, and discuss the limitations of current research and future research needs, providing a scientific and reliable basis and perspective for further clinical application and promotion.

15.
Biochim Biophys Acta Mol Cell Res ; 1870(2): 119409, 2023 02.
Article En | MEDLINE | ID: mdl-36513218

ß1,4-galactosyltransferase-1 (ß4GalT1) is a type II membrane protein that catalyzes the transfer of galactose (Gal) from UDP-Gal to N-acetylglucosamine (GlcNAc) and forms a LacNAc structure. ß4GalT1 has a long form (termed ß4GalT1-L) and a short form (termed ß4GalT1-S) in mammalian cells. Although ß4GalT1 has been proven to play an important role in many biological and pathological processes, such as differentiation, immune responses and cancer development, the different functions of the two ß4GalT1 forms remain ambiguous. In this study, we demonstrated that total ß4GalT1 was upregulated in bladder cancer. Overexpression of ß4GalT1-S, but not ß4GalT1-L, increased drug resistance in bladder epithelial cells by upregulating p53 expression. Glycoproteomic analysis revealed that the substrate specificities of the two ß4GalT1 forms were different. Among the LacNAcylated proteins, the E3 ligase MDM2 could be preferentially modified by ß4GalT1-L compared to ß4GalT1-S, and this modification could increase the binding of MDM2 and p53 and further facilitate the degradation of p53. Our data proved that the two forms of ß4GalT1 could synergistically regulate p53-mediated cell survival under chemotherapy treatment. These results provide insights into the role of ß4GalT1-L and ß4GalT1-S and suggest their differentially important implications in the development of bladder cancer.


Tumor Suppressor Protein p53 , Urinary Bladder Neoplasms , Animals , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Urinary Bladder/metabolism , Ubiquitin-Protein Ligases/metabolism , Epithelial Cells/metabolism , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Mammals/metabolism
16.
Leukemia ; 37(1): 113-121, 2023 01.
Article En | MEDLINE | ID: mdl-36335262

Bone marrow (BM) stroma plays key roles in supporting hematopoietic stem cell (HSC) growth. Glycosylation contributes to the interactions between HSC and surrounding microenvironment. We observed that bisecting N-acetylglucosamine (GlcNAc) structures, in BM stromal cells were significantly lower for MDS/AML patients than for healthy subjects. Malignant clonal cells delivered exosomal miR-188-5p to recipient stromal cells, where it suppressed bisecting GlcNAc by targeting MGAT3 gene. Proteomic analysis revealed reduced GlcNAc structures and enhanced expression of MCAM, a marker of BM niche. We characterized MCAM as a bisecting GlcNAc-bearing target protein, and identified Asn 56 as bisecting GlcNAc modification site on MCAM. MCAM on stromal cell surface with reduced bisecting GlcNAc bound strongly to CD13 on myeloid cells, activated responding ERK signaling, and thereby promoted myeloid cell growth. Our findings, taken together, suggest a novel mechanism whereby MDS/AML clonal cells generate a self-permissive niche by modifying glycosylation level of stromal cells.


Leukemia, Myeloid, Acute , MicroRNAs , Humans , Bone Marrow/pathology , Proteomics , Hematopoietic Stem Cells/metabolism , Glycosylation , Leukemia, Myeloid, Acute/pathology , Tumor Microenvironment , CD146 Antigen/metabolism , MicroRNAs/metabolism
17.
Article En | MEDLINE | ID: mdl-36452136

The acupuncture case registry study is focusing on acupuncture therapy data from patient cases. The main objective is to collect real-world data and integrate clinically meaningful outcome evaluation indicators to uncover and evaluate real-world acupuncture efficacy and safety, explore factors affecting acupuncture efficacy, and provide real-world evidence to complement RCTs. Since the International Acupuncture Case Registry data collection system's establishment in 2017, 16 projects have been underway, including two acupuncture specialty therapies and 15 diseases. Data from 3404 patients included extensive information on the diagnosis and treatment of acupuncture and the evaluation of its efficacy. In order to serve as a guide for future studies, this article discusses the value of and rationale for establishing acupuncture case registry studies, how to distinguish them from patient registries, and crucial techniques for implementing registry studies in terms of applications, patient recruitment, costakeholder collaboration, data collection and management, study quality control, and ethics.

18.
Org Biomol Chem ; 20(47): 9392-9396, 2022 12 07.
Article En | MEDLINE | ID: mdl-36398442

A novel palladium catalyzed homodimerization of ortho-hydroxyphenyl substituted p-QMs has been developed via [4 + 2] cycloaddition/oxidative dehydrogenation coupling domino reactions. An interesting palladium catalyzed intramolecular benzyl C-H oxidation dehydrogenation to form a transannular C(sp3)-O bond was found. This protocol provided an efficient method to construct various dibenzodioxo[3.3.1]nonanes bearing spirocyclohexadienones.


Palladium
19.
Langmuir ; 38(48): 14981-14987, 2022 Dec 06.
Article En | MEDLINE | ID: mdl-36395357

Capturing the surface-structural dynamics of metal electrocatalysts under certain electrochemical environments is intriguingly desired for understanding the behavior of various metal-based electrocatalysts. However, in situ monitoring of the evolution of a polycrystalline metal surface at the interface of electrode-electrolyte solutions at negative/positive potentials with high-resolution scanning tunneling microscopy (STM) is seldom. Here, we use electrochemical STM (EC-STM) for in situ monitoring of the surface evolution process of a silver electrode in both an aqueous sodium hydroxide solution and an ionic liquid of 1-methyl-1-octylpyrrolidinium bis(trifluoromethylsulfonyl) amide driven by negative potentials. We found silver underwent a surface change from a polycrystalline structure to a well-defined surface arrangement in both electrolytes. In NaOH aqueous solution, the silver surface transferred in several minutes at a turning-point potential where hydrogen adsorbed and formed mainly (111) and (100) pits. Controversially, the surface evolution in the ionic liquid was much slower than that in the aqueous solution, and cation adsorption was observed in a wide potential range. The surface evolution of silver is proposed to be linked to the surface adsorbates as well as the formation of their complexes with undercoordinated silver atoms. The results also show that cathodic annealing of polycrystalline silver is a cheap, easy, and reliable way to obtain quasi-ordered crystal surfaces.

20.
Biomolecules ; 12(10)2022 10 09.
Article En | MEDLINE | ID: mdl-36291656

Cytarabine (Ara-C) has been one of the frontline therapies for clonal hematopoietic stem cell disorders, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but Ara-C resistance often occurs and leads to treatment failure. Exosomal microRNAs (miRNAs, miRs) as small noncoding RNA that play important roles in post-transcriptional gene regulation, can be delivered into recipient cells by exosomes and regulate target genes' expression. miR92a has been reported to be dysregulated in many cancers, including MDS and AML. However, the effects of exosomal miR92a in hematologic malignancies have not been fully investigated. In this study, qualitative analysis showed the significantly enhanced expression of exosomal miR92a in MDS/AML plasma. Subsequent functional assays indicated that exosomal miR92a can be transported and downregulate PTEN in recipient cells and, furthermore, activate the Wnt/ß-catenin signaling pathway and interfere with the Ara-C resistance of receipt MDS/AML cells in vitro and in vivo. Altogether, our findings offer novel insights into plasma exosomal miR92a participating in Ara-C resistance in MDS/AML and we propose miR92a as a potential therapeutic target for MDS/AML.


Leukemia, Myeloid, Acute , MicroRNAs , Myelodysplastic Syndromes , Humans , Cytarabine/pharmacology , beta Catenin/genetics , beta Catenin/metabolism , Wnt Signaling Pathway/genetics , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/metabolism , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , MicroRNAs/genetics , MicroRNAs/therapeutic use
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