Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 564
Filter
1.
Int J Ophthalmol ; 17(3): 570-576, 2024.
Article in English | MEDLINE | ID: mdl-38721501

ABSTRACT

AIM: To explore the combined application of surgical navigation nasal endoscopy (NNE) and three-dimensional printing technology (3DPT) for the adjunctive treatment of orbital blowout fractures (OBF). METHODS: Retrospective analysis was conducted on the data of patients with OBF who underwent surgical treatment at the Affiliated Eye Hospital of Nanchang University between July 2012 and November 2022. The control group consisted of patients who received traditional surgical treatment (n=43), while the new surgical group (n=52) consisted of patients who received NNE with 3DPT. The difference in therapeutic effects between the two groups was evaluated by comparing the duration of the operation, best corrected visual acuity (BCVA), enophthalmos difference, recovery rate of eye movement disorder, recovery rate of diplopia, and incidence of postoperative complications. RESULTS: The study included 95 cases (95 eyes), with 63 men and 32 women. The patients' age ranged from 5 to 67y (35.21±15.75y). The new surgical group and the control group exhibited no statistically significant differences in the duration of the operation, BCVA and enophthalmos difference. The recovery rates of diplopia in the new surgical group were significantly higher than those in the control group at 1mo [OR=0.03, 95%CI (0.01-0.15), P<0.0000] and 3mo [OR=0.11, 95%CI (0.03-0.36), P<0.0000] post-operation. Additionally, the recovery rates of eye movement disorders at 1 and 3mo after surgery were OR=0.08, 95%CI (0.03-0.24), P<0.0000; and OR=0.01, 95%CI (0.00-0.18), P<0.0000. The incidence of postoperative complications was lower in the new surgical group compared to the control group [OR=4.86, 95%CI (0.95-24.78), P<0.05]. CONCLUSION: The combination of NNE and 3DPT can shorten the recovery time of diplopia and eye movement disorder in patients with OBF.

2.
J Hazard Mater ; 469: 133531, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38447361

ABSTRACT

Due to the widely discharge of chromium (Cr) by mining and smelting industries, etc., contamination of paddy soils and rice has become serious problems. Therefore it is crucial to explore how rice takes up Cr. Cr(III) is the most common Cr form in the long-term water flooding paddy soils. Here, we demonstrate that OsYSL15, a key gene for Fe(III) uptake, is equally applicable for Cr(III) uptake in rice. Firstly, the antagonistic effect of Cr(III) and Fe(III) in the uptake process was found. Rice could accumulate more Cr(III) under Fe-deficient conditions. And the Fe(III) content in the protoplasts of rice root cells gradually decreased with the increase exposure of Cr(III). Knockdown of OsYSL15 in rice significantly reduced the Cr(III) uptake rate. Compared with wild type rice, the accumulation of Cr(III) in OsYSL15 mutant was decreased by 40.7%- 70.6% after gene editing. These results indicate that OsYSL15 is a key gene responsible for Cr(III) uptake in rice, which can guide the screening or genetic modification for low-Cr-accumulation rice varieties.


Subject(s)
Oryza , Soil Pollutants , Chromium/metabolism , Oryza/metabolism , Iron/metabolism , Biological Transport , Membrane Transport Proteins , Soil , Soil Pollutants/analysis
3.
Chem Sci ; 15(11): 3971-3979, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38487230

ABSTRACT

Photo-responsive materials can convert light energy into mechanical energy, with great application potential in biomedicine, flexible electronic devices, and bionic systems. We combined reversible amide bonds, coordination site regulation, and coordination polymer (CP) self-assembly to synthesize two 1D photo-responsive CPs. Obvious photomechanical behavior was observed under UV irradiation. By combining the CPs with PVA, the mechanical stresses were amplified and macroscopic driving behavior was realized. In addition, two cyclobutane amide derivatives and a pair of cyclobutane carboxyl isomers were isolated through coordination bond destruction and amide bond hydrolysis. Therefore, photo-actuators and supramolecular synthesis in smart materials may serve as important clues.

4.
Int J Biol Macromol ; 265(Pt 1): 130791, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479666

ABSTRACT

The combination of straw returning and nitrogen (N) fertilization is a popular tillage mode and essential strategy for achieving stable yield and high quality. However, the optimal combination strategy and the influence of tillage mode on the morphological, crystalline, and molecular structures of maize starch remain unclear. We conducted a long-term field experiment over 7 years in Northeast China using two tillage modes, rotary tillage with straw returning (RTS) and plow tillage with straw returning (PTS), and four N application rates. The relative crystallinity, 1045/1022 cm-1 value, and B2 and B3 chains of maize starch were higher under RTS than under PTS, resulting in increased stability of starch and improvements in gelatinization enthalpy and temperature. The surface of the starch granules induced by N fertilizer was smoother than that under the N0 (0 kg N ha-1) treatment. The proportion of amylose content, solubility, swelling power, and light transmittance increased under N2 (262 kg N ha-1) treatment, along with improvement in starch pasting properties. These results suggest that RTS combined with N2 treatment can regulate the morphological, structural, and physicochemical characteristics of maize starch, providing an essential reference for improving the quality of maize starch from an agronomic point of view.


Subject(s)
Nitrogen , Zea mays , Nitrogen/analysis , Agriculture/methods , Starch/chemistry , China , Fertilization , Soil/chemistry
5.
Lancet Haematol ; 11(5): e336-e344, 2024 May.
Article in English | MEDLINE | ID: mdl-38554717

ABSTRACT

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Asparaginase , Deoxycytidine , Gemcitabine , Lymphoma, Extranodal NK-T-Cell , Oxaliplatin , Polyethylene Glycols , Humans , Middle Aged , Asparaginase/therapeutic use , Asparaginase/adverse effects , Asparaginase/administration & dosage , Male , Lymphoma, Extranodal NK-T-Cell/drug therapy , Lymphoma, Extranodal NK-T-Cell/mortality , Female , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Polyethylene Glycols/therapeutic use , Polyethylene Glycols/adverse effects , Polyethylene Glycols/administration & dosage , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Oxaliplatin/adverse effects , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Young Adult , Adolescent
6.
Inorg Chem ; 63(8): 3870-3881, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38356223

ABSTRACT

Metal-organic frameworks (MOFs) have shown promising potential as proton-conducting materials due to their tunable structures and high porosity. In this study, two novel MOFs had been successfully synthesized, one containing sulfate groups (MOF-1; [Zn4(TIPE)2(SO4)4(H2O)]·5H2O) and the other containing sulfonate groups (MOF-2; [Zn2(TIPE)(5-sip)(NO3)0.66]·0.34NO3·17.5H2O) (TIPE = 1,1,2,2-tetrakis(4-(1H-imidazole-1-yl)phenyl)ethene, H35-sip = 5-sulfoisophthalicacid), and the effect of the two groups on the proton conductivity of Zn-based MOFs had been investigated and compared for the first time. The proton conductivity of these MOFs was systematically measured at different temperatures and humidity conditions. Remarkably, the results revealed significant differences in proton conductivity between the two sets of MOFs. At 90 °C and 98% RH, MOF-1 and MOF-2 achieved optimal proton conductivity of 4.48 × 10-3 and 5.69 × 10-2 S·cm-1, respectively. This was due to the structural differences arising from the presence of different functional groups, which subsequently affected the porosity and hydrophilicity, thereby influencing the proton conductivity. Overall, this comparative study revealed the influence of sulfate and sulfonate groups on the proton conductivity of Zn-based MOFs. This research provided a feasible idea for the development of advanced MOF materials with enhanced proton conductivity and opened up new possibilities for their application in proton devices.

7.
Pest Manag Sci ; 80(6): 2587-2595, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38265118

ABSTRACT

BACKGROUND: Cry1Ab has emerged as a bio-insecticide to control Spodoptera litura (Lepidoptera: Noctuidae). However, the sublethal effects of Cry1Ab on the physiological changes and molecular level of S. litura have not been well documented. Our aims in this study were to assess the sublethal effect of Cry1Ab on S. litura, including midgut and Malpighian tubules as targets. RESULTS: After sublethal Cry1Ab exposure, distinct histological alterations were mainly observed in the midgut. Furthermore, the results of comparative RNA sequencing and tandem mass tag-based proteomics showed that, in the midgut, most differential expression genes (DEGs) were up-regulated and significantly enriched in the serine protease activity pathway, and up-regulated differential expression proteins (DEPs) were mainly associated with the oxidative phosphorylation pathway, whereas the down-regulated involved in the ribosome pathways. In the Malpighian tubules, DEGs and DEPs were significantly enriched in the ribosome pathway. We proposed that ribosome may act as a universal target in energy metabolism with other pathways via the results of protein-protein interaction analysis. Further, by verification of the mRNA expression of some Cry protein receptor and detoxification genes after Cry1Ab treatment, it was suggested that the ribosomal proteins (RPs) possibly participate in influencing the Bt-resistance of S. litura larvae under sublethal Cry1Ab exposure. CONCLUSION: Under sublethal Cry1Ab exposure, the midgut of S. litura was damaged, and the proteotranscriptomic analysis elucidated that Cry1Ab disrupted the energy homeostasis of larvae. Furthermore, we emphasized the potential role of ribosomes in sublethal Cry1Ab exposure. © 2024 Society of Chemical Industry.


Subject(s)
Bacillus thuringiensis Toxins , Endotoxins , Hemolysin Proteins , Larva , Malpighian Tubules , Spodoptera , Animals , Spodoptera/drug effects , Spodoptera/genetics , Spodoptera/metabolism , Spodoptera/growth & development , Malpighian Tubules/drug effects , Malpighian Tubules/metabolism , Larva/drug effects , Larva/genetics , Larva/growth & development , Larva/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Insect Proteins/metabolism , Insect Proteins/genetics , Transcriptome , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Insecticides/toxicity , Proteome , Proteomics , Digestive System/drug effects , Digestive System/metabolism
8.
Mol Divers ; 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38240951

ABSTRACT

Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.

9.
Adv Sci (Weinh) ; 11(7): e2306143, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38083984

ABSTRACT

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.


Subject(s)
Arthritis , Macrophages , Humans , Macrophages/metabolism , Arthritis/drug therapy , Phagocytosis , Anti-Inflammatory Agents/therapeutic use , Cell Communication
10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013605

ABSTRACT

Aim To investigate the mechanism of curcumin inhibition of oxidative stress on osteogenic differentiation and its dose-dependent anti-osteoporosis effect. Methods Cellular oxidative stress models were used, different concentrations of curcumin were added to determinethebone formation markers, and the potential signaling pathways involvedwere detected. Meanwhile, the mouse model of osteoporosis ( ovariecto- mized, 0VX) was used to confirm its effect against osteoporosis. Results In vitro experiments found that low concentrations of curcumin (1-10 μmol · L

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013597

ABSTRACT

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

12.
Clin Transl Med ; 13(12): e1505, 2023 12.
Article in English | MEDLINE | ID: mdl-38082402

ABSTRACT

BACKGROUND: Epstein-Barr virus-associated gastric cancer (EBVaGC) is regarded as a distinct molecular subtype of GC, accounting for approximately 9% of all GC cases. Clinically, EBVaGC patients are found to have a significantly lower frequency of lymph node metastasis and better prognosis than uninfected individuals. RNA N6-methyladenosine (m6A) modification has an indispensable role in modulating tumour progression in various cancer types. However, its impact on EBVaGC remains unclear. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and m6A dot blot were conducted to compare the m6A modification levels between EBVaGC and EBV-negative GC (EBVnGC) cells. Western blot, real-time quantitative PCR (RT-qPCR) and immunohistochemistry were applied to explore the underlying mechanism of the reduced m6A modification in EBVaGC. The biological function of fat mass and obesity-associated protein (FTO) was determined in vivo and in vitro. The target genes of FTO were screened by MeRIP-seq, RT-qPCR and Western blot. The m6A binding proteins of target genes were verified by RNA pulldown and RNA immunoprecipitation assays. Chromatin immunoprecipitation and Luciferase report assays were performed to investigate the mechanism how EBV up-regulated FTO expression. RESULTS: M6A demethylase FTO was notably increased in EBVaGC, leading to a reduction in m6A modification, and higher FTO expression was associated with better clinical outcomes. Furthermore, FTO depressed EBVaGC cell metastasis and aggressiveness by reducing the expression of target gene AP-1 transcription factor subunit (FOS). Methylated FOS mRNA was specifically recognized by the m6A 'reader' insulin-like growth factor 2 mRNA binding protein 1/2 (IGF2BP1/2), which enhanced its transcripts stability. Moreover, MYC activated by EBV in EBVaGC elevated FTO expression by binding to a specific region of the FTO promoter. CONCLUSIONS: Mechanistically, our work uncovered a crucial suppressive role of FTO in EBVaGC metastasis and invasiveness via an m6A-FOS-IGF2BP1/2-dependent manner, suggesting a promising biomarker panel for GC metastatic prediction and therapy.


Subject(s)
Epstein-Barr Virus Infections , Stomach Neoplasms , Humans , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/genetics , RNA , RNA, Messenger/genetics , Stomach Neoplasms/pathology , Up-Regulation/genetics
13.
Discov Nano ; 18(1): 144, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37999909

ABSTRACT

Atmospheric plasma processing, which combines the efficacy of chemical processes and the safety of physical processes, has been used to modify the surface characteristics of graphite-based materials. In this work, two distinct plasma source gases, C4F8 and O2, with the addition of a rotary reactor were used. The effectiveness of modifying the basal plane of intercalated graphite nanoplatelets (GnP) was investigated with various analytical techniques and the visual observation of the dispersion of these plasma-treated GnP in solvents was also reported. It is shown that this low-temperature plasma processing technique can be used to successfully modify the GnP surface without significantly changing the intrinsic structure of the GnP, which is desirable in many applications. With the C4F8 plasma treatment, the immersion characteristics in solvents can be tuned and the functional groups present on the surface can be tailored to produce desired bonding environments. This surface chemistry tunability will provide the needed functionalities in creating graphene-containing composite materials.

14.
Dalton Trans ; 52(43): 15940-15949, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37843307

ABSTRACT

Anions play a significant role in the construction of metal-organic frameworks (MOFs). Anions can affect coordination between metal ions and organic ligands, and the formation of crystal structures, thereby affecting the structure and properties of MOFs. Two novel 3D porous MOFs ({[Cd3(TIPE)2(SO4)1.6(H2O)2.4]·2.8OH·6.2H2O}n (MOF-1) and {[Cd3(TIPE)2(SO4)3(H2O)2]·10H2O}n (MOF-2)) were successfully synthesized, by introducing SO42- to design and adjust their structure and properties, in which the sulfate ions not only participated in coordination but also played a bridging role. Both MOF-1 and MOF-2 exhibited high stability and strong fluorescence properties, and their fluorescence properties also changed compared to those of previously reported 2D nonporous MOF-3 ({[Cd2(TIPE)2Cl3(ACN)]·CdCl3·3H2O}n) with an identical ligand. They could also be used in combination with MOF-3 to distinguish between Fe3+ and Cr2O72- ions, due to a change in their fluorescence properties. In this work, the structure was reshaped by introducing sulfate ions, and the role and function of the sulfate ions in the structure were studied, providing a feasible idea for the design and precise regulation of MOFs.

15.
Langmuir ; 39(38): 13688-13694, 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37683112

ABSTRACT

In this work, a "fish cage" material for trapping Pb(II) ions has been successfully obtained, which is a novel clathrate functionalized metal-oganic framework (Cage-MOF) by introducing free adsorption sites (SO42-). The three-dimensional (3D) cage structure of Cage-MOF gives it a larger contact area and can capture "swimming fish" (Pb(II)) like a "fishing cage" in a water solution. This is the first high-efficiency adsorption material obtained by introducing free coordination groups. Cage-MOF not only has excellent water stability but also improves the selectivity and affinity for Pb(II) ions in water because of the presence of sulfate adsorption sites, and its adsorption capacity is as high as 806 mg/g. This work shows a novel and effective idea for the synthesis of water restoration materials.

16.
Clin Transl Med ; 13(9): e1410, 2023 09.
Article in English | MEDLINE | ID: mdl-37712124

ABSTRACT

BACKGROUND: Predictive biomarkers for oesophageal squamous cell carcinoma (ESCC) immunotherapy are lacking, and immunotherapy resistance remains to be addressed. The role of long noncoding RNA (lncRNA) in ESCC immune escape and immunotherapy resistance remains to be elucidated. METHODS: The tumour-associated macrophage-upregulated lncRNAs and the exosomal lncRNAs highly expressed in ESCC immunotherapy nonresponders were identified by lncRNA sequencing and polymerase chain reaction assays. CRISPR-Cas9 was used to explore the functional roles of the lncRNA. RNA pull-down, MS2-tagged RNA affinity purification (MS2-TRAP) and RNA-binding protein immunoprecipitation (RIP) were performed to identify lncRNA-associated proteins and related mechanisms. In vivo, the humanized PBMC (hu-PBMC) mouse model was established to assess the therapeutic responses of specific lncRNA inhibitors and their combination with programmed cell death protein 1 (PD-1) monoclonal antibody (mAb). Single-cell sequencing, flow cytometry, and multiplex fluorescent immunohistochemistry were used to analyze immune cells infiltrating the tumour microenvironment. RESULTS: We identified a lncRNA that is involved in tumour immune evasion and immunotherapy resistance. High LINC02096 (RIME) expression in plasma exosomes correlates with a reduced response to PD-1 mAb treatment and poor prognosis. Mechanistically, RIME binds to mixed lineage leukaemia protein-1 (MLL1) and prevents ankyrin repeat and SOCS box containing 2 (ASB2)-mediated MLL1 ubiquitination, improving the stability of MLL1. RIME-MLL1 increases H3K4me3 levels in the promoter regions of programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO-1), constitutively increasing the expression of PD-L1/IDO-1 in tumour cells and inhibiting CD8+ T cells infiltration and activation. RIME depletion in huPBMC-NOG mice significantly represses tumour development and improves the effectiveness of PD-1 mAb treatment by activating T-cell-mediated antitumour immunity. CONCLUSIONS: This study reveals that the RIME-MLL1-H3K4me3 axis plays a critical role in tumour immunosuppression. Moreover, RIME appears to be a potential prognostic biomarker for immunotherapy and developing drugs that target RIME may be a new therapeutic strategy that overcomes immunotherapy resistance and benefits patients with ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , RNA, Long Noncoding , Animals , Mice , Antibodies, Monoclonal , B7-H1 Antigen/genetics , CD8-Positive T-Lymphocytes , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Leukocytes, Mononuclear , Myeloid-Lymphoid Leukemia Protein , Programmed Cell Death 1 Receptor , RNA, Long Noncoding/genetics , Tumor Microenvironment/genetics
17.
J Hematol Oncol ; 16(1): 78, 2023 07 22.
Article in English | MEDLINE | ID: mdl-37480137

ABSTRACT

The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.


Subject(s)
Epstein-Barr Virus Infections , Lymphoma, T-Cell , Lymphoma , Humans , Herpesvirus 4, Human , Killer Cells, Natural
18.
Small ; 19(48): e2303802, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37519121

ABSTRACT

The volume expansion of CoFe2 O4 anode poses a significant challenge in the commercial application of lithium/sodium-ion batteries (LIBs/SIBs). However, metal-organic-frameworks (MOF) offer superior construction of heterostructures with refined interfacial interactions and lower ion diffusion barriers in Li/Na storage. In this study, the CoFe2 O4 @carbon nanofibers derived from MOF are produced through electrospinning, in situ growth followed by calcination, which are then confined within an MXene-confined MOF-derived porous CoFe2 O4 @carbon composite architecture under alkali treatment. The CoFe2 O4 nanofibers anchor on the alkalized MXene that is decorated with the NaOH solution to form a multi-pleated structure. The sandwich-like structure of the composite effectively alleviates the volume expansion and shortens the Li/Na-ion diffusion path, which displays high capacity and outstanding rate performance as anode materials for LIBs/SIBs. As a consequence, the obtained CoFe2 O4 @carbon@alkalized MXene composite anode shows satisfied rate performance at current density of 10 A g-1 for LIBs (318 mAh·g-1 ) and 5 A g-1 for SIBs (149 mAh g-1 ). The excellent cycling performance is further demonstrated at a high current density, where it maintains a discharge capacity of 807 mAh g-1 at 2 A g-1 after 400 cycles for LIBs and 130 mAh g-1 at 1 A g-1 even after 1000 cycles for SIBs.

19.
ACS Appl Mater Interfaces ; 15(24): 29102-29109, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37294824

ABSTRACT

Ultra-thin silver films are susceptible to ambient environments and form grayish layers in the silver mirroring process. The poor wettability together with the high diffusivity of surface atoms in the presence of oxygen accounts for the thermal instability of ultra-thin silver films in the air and at elevated temperatures. This work demonstrates an atomic-scale aluminum cap layer on the silver to enhance the thermal and environmental stabilities of ultra-thin silver films deposited by sputtering with the assistance of a soft ion beam reported in our previous work. The resulted film consists of an ion-beam-treated seed silver layer of ∼1 nm nominal thickness, a subsequent silver layer of ∼6 nm thickness produced by sputtering alone, and an aluminum cap layer of ∼0.2 nm nominal thickness. Although the aluminum cap is only one to two atomic layers and likely non-continuous, it significantly improved the thermal and ambient environmental stability of the ultra-thin silver films (∼7 nm thick) without affecting the film's optical and electrical properties. The improved environmental stability is attributed to the cathodic protection mechanism and reduced diffusivity of surface atoms. The improved thermal stability is attributed to the reduced mobility of surface atoms in the presence of aluminum atoms. Thermal treatment of the duplex film also improves the film's electrical conductivity and optical transmittance by enhancing its crystallinity. The annealed aluminum/silver duplex structure has exhibited the lowest electric resistivity among the reported ultra-thin silver films and high optical transmittance similar to the simulated theoretical results.

20.
J Inorg Biochem ; 246: 112293, 2023 09.
Article in English | MEDLINE | ID: mdl-37354605

ABSTRACT

A series of O-phenanthroline silver(I) complexes were synthesized and characterized by infrared (IR) spectroscopy, mass spectrometry (MS), 1H nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography. The cytotoxicity of the silver(I) complex (P-131) was evaluated in the cancer cell lines HCT-116, HeLa, and MDA-MB-231 and the normal cell line LO2 via MTT assays. The 50% inhibition concentration (IC50) of P-131 on HCT116 cell line is 0.86 ± 0.03 µM. It is far lower than the IC50 value of cisplatin (9.08 ± 1.10 µM), the IC50 value of normal cell LO2 (76.20 ± 0.48 µM) is much higher than that of cisplatin (3.99 ± 0.74 µM), indicating that its anticancer effect is stronger than that of cisplatin, and its biological safety is greater than that of cisplatin. Furthermore, anticancer mechanistic studies showed that P-131 inhibited cell proliferation by blocking DNA synthesis and acted temporally on the nucleus in dividing HCT-116 cells. Moreover, P-131 increased intracellular reactive oxygen species (ROS) levels in a dose-dependent manner. Notably, 10 mg/kg P-131 showed better antitumor effects than oxaliplatin in an HCT116 human colorectal xenograft mouse model without inducing toxicity. Moreover, the microdilution broth method was used to evaluate the antimicrobial properties of P-131 against Pseudomonas aeruginosa and Candida albicans. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy.


Subject(s)
Adenocarcinoma , Anti-Infective Agents , Antineoplastic Agents , Colorectal Neoplasms , Coordination Complexes , Humans , Animals , Mice , Cisplatin/pharmacology , Silver/pharmacology , Silver/chemistry , Anti-Infective Agents/pharmacology , HeLa Cells , Colorectal Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Cell Proliferation , Cell Line, Tumor
SELECTION OF CITATIONS
SEARCH DETAIL
...