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1.
Bioinorg Chem Appl ; 2024: 6618388, 2024.
Article in English | MEDLINE | ID: mdl-38333411

ABSTRACT

Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.

2.
Redox Biol ; 69: 102996, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38103341

ABSTRACT

Diabetic encephalopathy (DE) is a common central nervous system complication of diabetes mellitus without effective therapy currently. Recent studies have highlighted synaptic mitochondrial damages as a possible pathological basis for DE, but the underlying mechanisms remain unclear. Our previous work has revealed that phosphatidate phosphatase Lipin1, a critical enzyme involved with phospholipid synthesis, is closely related to the pathogenesis of DE. Here, we demonstrate that Lipin1 is significantly down-regulated in rat hippocampus of DE. Knock-down of Lipin1 within hippocampus of normal rats induces dysregulation of homeostasis in synaptic mitochondrial dynamics with an increase of mitochondrial fission and a decrease of fusion, then causes synaptic mitochondrial dysfunction, synaptic plasticity deficits as well as cognitive impairments, similar to that observed in response to chronic hyperglycemia exposure. In contrast, an up-regulation of Lipin1 within hippocampus in the DE model ameliorates this cascade of dysfunction. We also find that the effect of Lipin1 that regulating mitochondrial dynamics results from maintaining appropriate phospholipid components in the mitochondrial membrane. In conclusion, alterations in hippocampal Lipin1 contribute to hippocampal synaptic mitochondrial dysfunction and cognitive deficits observed in DE. Targeting Lipin1 might be a potential therapeutic strategy for the clinical treatment of DE.


Subject(s)
Brain Diseases , Diabetes Mellitus , Hypoglycemia , Mitochondrial Diseases , Animals , Rats , Hippocampus/metabolism , Mitochondrial Dynamics , Phosphatidate Phosphatase/genetics , Phosphatidate Phosphatase/metabolism , Phospholipids
3.
Exp Hematol ; 128: 67-76, 2023 12.
Article in English | MEDLINE | ID: mdl-37739208

ABSTRACT

Risk stratification for normal karyotype acute myeloid leukemia (NK-AML) remains unsatisfactory, which is reflected by the high incidence of leukemia relapse. This study aimed to evaluate the role of gene mutations and clinical characterization in predicting the relapse of patients with NK-AML. A prognostic system for NK-AML was constructed. A panel of gene mutations was explored using next-generation sequencing. A nomogram algorithm was used to build a genomic mutation signature (GMS) nomogram (GMSN) model that combines GMS, measurable residual disease, and clinical factors to predict relapse in 347 patients with NK-AML from four centers. Patients in the GMS-high group had a higher 5-year incidence of relapse than those in the GMS-low group (p < 0.001). The 5-year incidence of relapse was also higher in patients in the GMSN-high group than in those in the GMSN-intermediate and -low groups (p < 0.001). The 5-year disease-free survival and overall survival rates were lower in patients in the GMSN-high group than in those in the GMSN-intermediate and -low groups (p < 0.001) as confirmed by training and validation cohorts. This study illustrates the potential of GMSN as a predictor of NK-AML relapse.


Subject(s)
Leukemia, Myeloid, Acute , Nucleophosmin , Humans , Mutation , Prognosis , Chronic Disease , Leukemia, Myeloid, Acute/genetics , Recurrence , Karyotype
4.
Environ Sci Pollut Res Int ; 30(35): 84437-84451, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37368213

ABSTRACT

A novel Fe-Mn binary oxide (FMBO)/bone char composite (FMBC) was synthesized and utilized to simultaneously adsorb Sb(III) and Cd(II) from aqueous phase in this study. The successful loading of Fe-Mn binary oxide on the bone char surface was revealed by the results of scanning electron microscope, X-ray diffraction patterns, and energy dispersive spectroscopy of FMBC. The FMBC exhibited remarkable ability of simultaneous removing Sb(III) and Cd(II) from aqueous, and the presence of Cd(II) enhanced Langmuir theoretical maximum adsorption capacity for Sb(III) significantly from 67.8 to 209.0 mg/g. Besides, FMBC could efficiently remove Sb(III) and Cd(II) in the wide initial pH range of 2-7. The influences of ionic strength, co-existing anions, humic acid, and temperature on the adsorption of Sb(III) and Cd(II), and the application potential of FMBC in actual groundwater were investigated. The main mechanisms of Sb(III) and Cd(II) adsorption onto FMBC involved redox, electrostatic interaction, surface complexation, ion exchange, and precipitation. The result of X-ray photoelectron spectroscopy and mapping spectrum analysis revealed that Mn(III) on FMBC played the key role in the Sb(III) oxidation, while FeOOH worked as the adsorption sites of FMBC. Meanwhile, the hydroxyapatite on FMBC also contributed to the removal of Cd(II). The presence of Cd(II) not only increased the positive charge on the surface of FMBC but also formed the Fe-Sb-Cd ternary complex, promoting the removal of Sb. This work provides valuable information for the application of FMBO/bone char as a cost-effective adsorbent to remediate co-pollution of Sb(III) and Cd(II) in aqueous environment.


Subject(s)
Oxides , Water Pollutants, Chemical , Oxides/chemistry , Water , Cadmium , Oxidation-Reduction , Temperature , Adsorption , Water Pollutants, Chemical/analysis
5.
J Environ Sci (China) ; 130: 197-211, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37032036

ABSTRACT

Recently, transition metal sulfides have attracted much attention due to their better catalytic capacities as peroxymonosulfate (PMS) activator than their metal oxide counterparts. However, the systematic studies on PMS activation using transition metal sulfides are still lacking. In this work, manganese sulfide (MnS) materials were synthesized via a MOFs-derived method and utilized for PMS activation to degrade levofloxacin (LVF) in water for the first time. As expected, MnS exhibited remarkable LVF degradation efficiency by PMS activation, which was distinctly higher than Mn2O3. The results of quenching experiments, electro spin resonance identification and electrochemical tests indicated that electron-transfer progress was the dominant mechanism in α-MnS/PMS system. Meanwhile, the presence of 1O2 and radicals further became the removal of LVF by α-MnS/PMS system into a radical/nonradical coupling process. The superior electrical conductivity of α-MnS than α-Mn2O3 was revealed by DFT calculations, which resulted in the higher catalytic capacity of α-MnS. The result of XPS also indicated the S species in MnS accelerated the recycle of Mn(IV)/Mn(II) and then promoted the generation of radicals. Furthermore, the influence of various environmental conditions on LVF removal and the reusability of α-MnS were also investigated, which demonstrated the high application potential of α-MnS/PMS system. Finally, six possible pathways of LVF oxidation in the system were proposed based on the identified byproducts and their ecotoxicity was evaluated with ECOSAR method. This work promotes the fundamental understanding of PMS activation by α-MnS and provides useful information for practical application of manganese sulfide in water treatment.


Subject(s)
Electrons , Levofloxacin , Peroxides , Sulfides
6.
Int Immunopharmacol ; 118: 109930, 2023 May.
Article in English | MEDLINE | ID: mdl-37001383

ABSTRACT

OBJECTIVES: Diabetic encephalopathy (DE) is a common complication of diabetes in the central nervous system, which can cause cognitive dysfunction in patients. However, its pathophysiological mechanism has not been elucidated, and thus effective prevention and treatment methods are still lacking.Previous studies reported that neuroinflammation involved in the central neuropathy, while lipin2 plays an important role in inflammatory response.Therefore, we aimed to investigate the effects of lipin2 on regulating inflammatory response in the pathogenesis of DE. METHODS: BV2 cells were treated with high glucose and infected with lipin2 overexpression or knockdown virus to observe the cell viability. Then, we constructed a mouse model of DE, and constructed a lipin2 knockdown or overexpression model by injecting lentivirus into the brain with stereotaxis. The expression of lipin2 in inflammatory bodies and related inflammatory factor signaling pathway-related proteins were examined by western blot and quantitative real-time PCR. Morris water maze was used to evaluate the spatial learning and memory of mice. RESULTS: High glucose decreased the expression of lipin2 in BV2 cells, while overexpression of lipin2 in BV2 cells significantly suppressed the inflammatory response and apoptosis induced by high glucose. Meanwhile, the expression of lipin2 was down-regulated in the hippocampus in a DE mice model. Up-regulation of lipin2 in the hippocampus of DE mice inhibited JNK/ERK signaling pathway, reduced NLRP3 inflammasome-mediated inflammatory response, down-regulated IL-1/TNF-α expression, and improved synaptic plasticity and cognitive dysfunction in mice. Conversely, knockdown of lipin2 increased NLRP3 inflammasome overactivation, caused neuronal abnormalities and cognitive impairment in mice. CONCLUSIONS: Lipin2 may play a neuroprotective role in DE by inhibiting JNK/ERK-mediated NLRP3 inflammasome overactivation and subsequent inflammatory responses. It may be a potential therapeutic target for DE therapy.


Subject(s)
Brain Diseases , Diabetes Mellitus , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Disease Models, Animal , Glucose
7.
Int J Hematol ; 116(6): 892-901, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36031670

ABSTRACT

OBJECTIVES: This study retrospectively investigated in which cycle measurable residual disease (MRD) is associated with prognosis in patients in first complete remission (CR1) of intermediate-risk acute myeloid leukemia (AML). METHODS: The study enrolled 235 younger patients with intermediate-risk AML. MRD was evaluated by multiparameter flow cytometry after the 1st, 2nd, and 3rd chemotherapy cycles (MRD1-3, respectively). RESULTS: No significant association was detected after the 1st and 2nd cycles. However, the 5-year incidence of relapse was higher in the MRD3-positive group (n = 99) than in the negative group (n = 136) (48.7% vs. 13.7%, P = 0.005), while 5-year disease-free survival (DFS) and overall survival (OS) were lower in the MRD3-positive group than in the negative group (43.2% vs. 81.0% and 45.4% vs. 84.1%; P = 0.003 and 0.005, respectively). Allogeneic hematopoietic stem cell transplantation led to a lower 5-year relapse, and higher DFS and OS rates than chemotherapy in the MRD3-positive group (22.3% vs. 71.5%, 65.9% vs. 23.0%, and 67.1% vs. 23.9%; P < 0.001, 0.002, and 0.022, respectively), but did not affect the MRD-negative group. CONCLUSIONS: MRD3 could serve as an indicator for post-remission treatment choice and help improve outcomes for intermediate-risk AML in CR1.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Transplantation, Homologous , Retrospective Studies , Leukemia, Myeloid, Acute/therapy , Neoplasm, Residual , Remission Induction , Prognosis , Recurrence , Receptors, Complement 3b
8.
Sci Total Environ ; 847: 157609, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35901891

ABSTRACT

Urban areas are the hardest hit by microplastic pollution, and deposition is an important part of microplastic migration and transport in the atmosphere, therefore, the study of microplastics in an urban atmospheric deposition is of great significance. This study aims to investigate the deposition characteristics of atmospheric microplastics in megapolis, to clarify the influence of meteorological and anthropogenic factors, and to analyze the sources of atmospheric microplastics. Six sampling sites in Shanghai were selected to collect atmospheric deposition samples during the rainy season. The mean deposition flux of microplastics was 3261.22 ± 2847.99 P·m-2·d-1 (median: 2559.70 P·m-2·d-1), and the types were mainly polyamide (PA, 27.79 %), polyethylene terephthalate (PET, 27.29 %), polypropylene (PP, 16.95 %), and polyvinyl fluoride (PVF, 12.88 %). The microplastic with the particle size of <1000 µm accounted for 88.23 %, and the shape was mainly fiber (73.55 %). The results of correlation analysis and variance analysis of microplastic characteristics with meteorological and anthropogenic factors (land-use, atmospheric pollutants, and urban indicators) showed that wind and precipitation had effects on deposition flux, size and shape, and were more significant at small scales (individual cities), while at large scales, the population was the main influence of microplastics. Atmospheric microplastics in Shanghai may be dominated by exogenous sources, through a combination of microplastic characteristics, wind and backward trajectories. This study further reveals the fate of urban atmospheric microplastics, which has implications for the study of global microplastic pollution.


Subject(s)
Environmental Pollutants , Water Pollutants, Chemical , China , Environmental Monitoring , Environmental Pollutants/analysis , Microplastics , Nylons , Plastics/analysis , Polyethylene Terephthalates , Polypropylenes/analysis , Seasons , Water Pollutants, Chemical/analysis
9.
IEEE Trans Image Process ; 31: 3713-3725, 2022.
Article in English | MEDLINE | ID: mdl-35594230

ABSTRACT

The performance of deep learning heavily depend on the quantity and quality of training data. But in many fields, well-annotated data are so difficult to collect, which makes the data scale hard to meet the needs of network training. To deal with this issue, a novel data augmentation method using the bitplane information recombination model (termed as BIRD) is proposed in this paper. Considering each bitplane can provide different structural information at different levels of detail, this method divides the internal hierarchical structure of a given image into different bitplanes, and reorganizes them by bitplane extraction, bitplane selection and bitplane recombination, to form an augmented data with different image details. This method can generate up to 62 times of the training data, for a given 8-bits image. In addition, this generalized method is model free, parameter free and easy to combine with various neural networks, without changing the original annotated data. Taking the task of target detection for remotely sensed images and classification for natural images as an example, experimental results on DOTA dataset and CIFAR-100 dataset demonstrated that, our proposed method is not only effective for data augmentation, but also helpful to improve the accuracy of target detection and image classification.

10.
J Hazard Mater ; 430: 127832, 2022 05 15.
Article in English | MEDLINE | ID: mdl-35150994

ABSTRACT

A novel B,N-decorated carbocatalyst (Fe@BPC-XBN) for peroxymonosulfate (PMS) activation was prepared by a simple pyrolysis method using the iron-based metal organic frameworks (Fe-MOF), boric acid and boron nitride (BN) as precursors. Fe@BPC-20BN removed 93.3% of bisphenol A (BPA) in 90 min compared to 64.9%, 82.1% and 83.5% with Fe@PC, Fe@BPC and Fe@PC-20BN, respectively, with 0.15 g/L catalyst and 1 mM PMS at initial pH of 7. The solo B-doping with boron acid on the Fe-MOF derived porous carbon enhanced its catalytic capacity; moreover, B, N co-doping with BN and boron acid as precursors further promoted the catalytic performance. The addition of BN not only provided more B, N catalytic centers but also improved the stability of the carbocatalyst. In addition, hydroxyl radicals, sulfate radicals, superoxide radicals, and singlet oxygen species were involved in the degradation of BPA. Fe species, -BCO2/-BC2O, pyridinic N, and pyrrolic N groups on the carbon matrix played the important roles in the BPA degradation. The outstanding catalytic performance of Fe@BPC-20BN could be attributed to the synergistic effects between iron nanoparticles and the B/N codoped carbon matrix. This study gives new insights into the design and preparation of high-efficient B,N-decorated carbocatalysts for environmental remediation.


Subject(s)
Benzhydryl Compounds , Peroxides , Boron Compounds , Phenols
11.
Materials (Basel) ; 14(21)2021 Oct 28.
Article in English | MEDLINE | ID: mdl-34772000

ABSTRACT

Monitoring gait patterns in daily life will provide a lot of biological information related to human health. At present, common gait pressure analysis systems, such as pressure platforms and in-shoe systems, adopt rigid sensors and are wired and uncomfortable. In this paper, a biomimetic porous graphene-SBR (styrene-butadiene rubber) pressure sensor (PGSPS) with high flexibility, sensitivity (1.05 kPa-1), and a wide measuring range (0-150 kPa) is designed and integrated into an insole system to collect, process, transmit, and display plantar pressure data for gait analysis in real-time via a smartphone. The system consists of 16 PGSPSs that were used to analyze different gait signals, including walking, running, and jumping, to verify its daily application range. After comparing the test results with a high-precision digital multimeter, the system is proven to be more portable and suitable for daily use, and the accuracy of the waveform meets the judgment requirements. The system can play an important role in monitoring the safety of the elderly, which is very helpful in today's society with an increasingly aging population. Furthermore, an intelligent gait diagnosis algorithm can be added to realize a smart gait monitoring system.

12.
Mol Neurobiol ; 58(11): 6049-6061, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34435332

ABSTRACT

Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes, and its neural mechanisms underlying the pathogenesis remain unclear. Autophagy plays an important role in neurodegenerative diseases and nerve tissue injury. Lipin1 is a phosphatidic acid phosphatase enzyme that converts phosphatidic acid (PA) into diacylglycerol (DAG), a precursor of triacylglycerol and phospholipids which plays an important role in maintaining normal peripheral nerve conduction function. However, whether Lipin1 involved in the pathogenesis of DPN via regulation of autophagy is not elucidated. Here, we show that the Lipin1 expression was downregulated in streptozotocin (STZ)-induced DPN rat model. Interestingly, STZ prevented DAG synthesis, and resulted in autophagic hyperactivity, effects which may increase the apoptosis of Schwann cells and lead to demyelination in sciatic nerve in DPN rats. More importantly, upregulation of lipin1 in the DPN rats ameliorated autophagy disorders and pathological changes of the sciatic nerve, which associated with the increase of the motor nerve conductive velocity (MNCV) in DPN rats. In contrast, knockdown of lipin1 exacerbates neuronal abnormalities and facilitates the genesis of DPN phenotypes in rats. In addition, overexpression of lipin1 in RSC96 cells also significantly decreased the autophagic hyperactivity and apoptosis induced by hyperglycemia. These results suggest that lipin1 may exert neuroprotection within the sciatic nerve anomalies and may serve as a potential therapeutic target for the treatment of DPN.


Subject(s)
Autophagy/physiology , Demyelinating Diseases/physiopathology , Diabetes Mellitus, Experimental/complications , Diabetic Neuropathies/physiopathology , Nerve Degeneration/physiopathology , Nuclear Proteins/physiology , Sciatic Nerve/physiopathology , Animals , Apoptosis , Cells, Cultured , Demyelinating Diseases/etiology , Demyelinating Diseases/therapy , Diabetes Mellitus, Experimental/blood , Diglycerides/biosynthesis , Down-Regulation , Gene Knockdown Techniques , Genetic Vectors/therapeutic use , Hyperalgesia/etiology , Hyperalgesia/therapy , Hyperglycemia/etiology , Hyperglycemia/metabolism , Male , Nerve Degeneration/etiology , Neural Conduction , Nuclear Proteins/biosynthesis , Nuclear Proteins/genetics , Nuclear Proteins/therapeutic use , Rats , Rats, Wistar , Recombinant Proteins/metabolism , Schwann Cells/metabolism
13.
Autophagy ; 17(5): 1170-1192, 2021 05.
Article in English | MEDLINE | ID: mdl-32324083

ABSTRACT

CTSD/CathD/CATD (cathepsin D) is a lysosomal aspartic protease. A distinguishing characteristic of CTSD is its dual functions of promoting cell proliferation via secreting a pro-enzyme outside the cells as a ligand, and promoting apoptosis via the mature form of this enzyme inside cells; however, the regulation of its secretion, expression, and maturation is undetermined. Using the lepidopteran insect Helicoverpa armigera, a serious agricultural pest, as a model, we revealed the dual functions and regulatory mechanisms of CTSD secretion, expression, and maturation. Glycosylation of asparagine 233 (N233) determined pro-CTSD secretion. The steroid hormone 20-hydroxyecdysone (20E) promoted CTSD expression. Macroautophagy/autophagy triggered CTSD maturation and localization inside midgut cells to activate CASP3 (caspase 3) and promote apoptosis. Pro-CTSD was expressed in the pupal epidermis and was secreted into the hemolymph to promote adult fat body endoreplication/endoreduplication, cell proliferation, and association. Our study revealed that the differential expression and autophagy-mediated maturation of CTSD in tissues determine its roles in apoptosis and cell proliferation, thereby determining the cell fates of tissues during lepidopteran metamorphosis.Abbreviations: 20E: 20-hydroxyecdysone; 3-MA: 3-methyladenine; ACTB/ß-actin: actin beta; AKT: protein kinase B; ATG1: autophagy-related 1; ATG4: autophagy-related 4; ATG5: autophagy-related 5; ATG7: autophagy-related 7; ATG14: autophagy-related 14; BSA: bovine serum albumin; CASP3: caspase 3; CQ: choroquine; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; DMSO: dimethyl sulfoxide; DPBS: dulbecco's phosphate-buffered saline; DsRNA: double-stranded RNA; EcR: ecdysone receptor; EcRE: ecdysone response element; EdU: 5-ethynyl-2´-deoxyuridine; G-m-CTSD: glycosylated-mautre-CTSD; G-pro-CTSD: glycosylated-pro-CTSD; HaEpi: Helicoverpa armigera epidermal cell line; HE staining: hematoxylin and eosin staining; IgG: immunoglobin G; IM: imaginal midgut; JH: juvenile hormone; Kr-h1: krueppel homologous protein 1; LM: larval midgut; M6P: mannose-6-phosphate; PBS: phosphate-buffered saline; PCD: programmed cell death; PNGase: peptide-N-glycosidase F; RFP: red fluorescent protein; RNAi: RNA interference; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SYX17: syntaxin 17; USP1: ultraspiracle isoform 1.


Subject(s)
Apoptosis/physiology , Autophagy/physiology , Cathepsin D/metabolism , Animals , Autophagy/genetics , Cell Proliferation/physiology , Ecdysterone/metabolism , Gene Knockdown Techniques , Lysosomes/metabolism , Receptors, Steroid/metabolism
14.
J Med Chem ; 64(1): 629-643, 2021 01 14.
Article in English | MEDLINE | ID: mdl-33381963

ABSTRACT

In a pancreatic tumor microenvironment, activated pancreatic stellate cells (PSCs) produce extracellular matrix (ECM) to form a barrier to drug penetration. Moreover, the interaction between cancer cells and activated PSCs promotes the tumor growth. Vitamin D receptor (VDR), as a key regulator to promote the recovery of PSCs to the resting state, is an attractive therapeutic target for pancreatic cancer. Herein, we reported the design and synthesis of 57 nonsecosteroidal VDR modulators based on the skeleton of phenyl-pyrrolyl pentane. Among them, compounds C4, I5, and I8 exhibited excellent VDR affinity and effective inhibition of the activation of PSCs, as well as potent suppression of the interaction between cancer cells and PSCs in vitro. In vivo, compound I5 combined with gemcitabine achieved efficacious antitumor activity without causing hypercalcemia. In conclusion, the compounds designed in our study can remodel the tumor microenvironment and are expected to be candidates for the treatment of pancreatic cancer.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Receptors, Calcitriol/agonists , Tumor Microenvironment/drug effects , Cell Proliferation/drug effects , Deoxycytidine/pharmacology , Humans , Pancreatic Neoplasms/pathology , Pancreatic Stellate Cells/drug effects , Pancreatic Stellate Cells/pathology , Gemcitabine
15.
Biosci Rep ; 40(10)2020 10 30.
Article in English | MEDLINE | ID: mdl-33006362

ABSTRACT

Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related mortality globally. However, the mechanism underlying NSCLC is not fully understood. Here, we investigated the role of cancer-related regulator of actin dynamics (CRAD) in NSCLC. We showed that CRAD was up-regulated in human NSCLC tissues and lung cancer cell lines. Lentivirus-mediated knockdown of CRAD repressed the proliferation and colony growth of A549 and H1299 cells. Apoptosis was enhanced by CRAD silencing in both cells, implicating that CRAD might maintain the survival of lung cancer cells. Microarray and bioinformatic assay revealed that CRAD directly or indirectly regulated diverse genes, including those involved in cell cycle and DNA damage repair. qRT-PCR and Western blot results confirmed the dysregulated genes as shown in microarray analysis. Claudin 4 was up-regulated in CRAD silenced A549 cells. The knockdown of Claudin 4 blocked the effects of CRAD on the expression of cell cycle and apoptosis effectors and enhanced the viability of A549 cells with CRAD down-regulation. Taken together, our findings demonstrate that CRAD acts as an oncogene in NSCLC at least partly through repressing Claudin 4.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Claudin-4/genetics , Lung Neoplasms/pathology , Microfilament Proteins/metabolism , A549 Cells , Apoptosis/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cell Cycle/genetics , Cell Proliferation/genetics , Computational Biology , DNA Damage , DNA Repair/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Lung/pathology , Lung Neoplasms/genetics , Microfilament Proteins/genetics , Oligonucleotide Array Sequence Analysis , Signal Transduction/genetics , Up-Regulation
16.
ACS Appl Mater Interfaces ; 12(16): 18375-18384, 2020 Apr 22.
Article in English | MEDLINE | ID: mdl-32223262

ABSTRACT

Intraocular pressure (IOP) is the prime indicator for the diagnosis and treatment of glaucoma. IOP has circadian rhythm changes and is dependent on body gestures; therefore, a single measurement in the clinic can be misleading for diagnosis. Herein, few-layer graphene is utilized to develop non-invasive sensors with high transparency, sensitivity, linearity, and biocompatibility for 24 h continuous IOP monitoring. The graphene Wheatstone bridge consisting of two strain gauges and two compensating resistors is designed to improve the sensitivity and accuracy of IOP measurement. Testing results on a silicone eyeball indicate that the output voltage of the sensor is proportional to the IOP fluctuation. Under the various ranges and speeds of IOP fluctuation, the sensor exhibits excellent performance of dynamic cycles and step responses with an average sensitivity of 150 µV/mmHg. With the linear relationship, the average relative error between the calibrated IOP and the standard pressure is maintained at about 5%. More than 100 cycles and interval time measurements illustrate that the sensor possesses significant stability, durability, and reliability. Furthermore, a wireless system is designed for the sensor to realize IOP monitoring using a mobile phone. This sensor, with the average transparency of 85% and its ease of fabrication, as well as its portability for continuous IOP monitoring, brings new promise to the diagnosis and treatment of glaucoma.


Subject(s)
Graphite/chemistry , Intraocular Pressure/physiology , Monitoring, Physiologic/instrumentation , Tonometry, Ocular/instrumentation , Equipment Design , Glaucoma/diagnosis , Humans , Models, Biological , Wireless Technology/instrumentation
17.
Article in English | MEDLINE | ID: mdl-32112680

ABSTRACT

Spectral or spatial dictionary has been widely used in fusing low-spatial-resolution hyperspectral (LH) images and high-spatial-resolution multispectral (HM) images. However, only using spectral dictionary is insufficient for preserving spatial information, and vice versa. To address this problem, a new LH and HM image fusion method termed OTD using optimized twin dictionaries is proposed in this paper. The fusion problem of OTD is formulated analytically in the framework of sparse representation, as an optimization of twin spectral-spatial dictionaries and their corresponding sparse coefficients. More specifically, the spectral dictionary representing the generalized spectrums and its spectral sparse coefficients are optimized by utilizing the observed LH and HM images in the spectral domain; and the spatial dictionary representing the spatial information and its spatial sparse coefficients are optimized by modeling the rest of high-frequency information in the spatial domain. In addition, without non-negative constraints, the alternating direction methods of multipliers (ADMM) are employed to implement the above optimization process. Comparison results with the related state-of-the-art fusion methods on various datasets demonstrate that our proposed OTD method achieves a better fusion performance in both spatial and spectral domains.

18.
Sensors (Basel) ; 20(3)2020 Feb 10.
Article in English | MEDLINE | ID: mdl-32050566

ABSTRACT

The floating height of the strip in an air cushion furnace is a key parameter for the quality and efficiency of production. However, the high temperature and high pressure of the working environment prevents the floating height from being directly measured. Furthermore, the strip has multiple floating states in the whole operation process. It is thus difficult to employ a single model to accurately describe the floating height in different states. This paper presents a multi-model soft sensor to estimate the height based on state identification and the soft transition. First, floating states were divided using a partition method that combined adaptive k-nearest neighbors and principal component analysis theories. Based on the identified results, a hybrid model for the stable state, involving a double-random forest model for the vibration state and a soft-transition model, was created to predict the strip floating height. In the hybrid model for the stable state, a mechanistic model combined thick jet theory and the equilibrium equation of force to cope with the lower floating height. In addition, a novel soft-transition model based on data gravitation that further reflects the intrinsic process characteristic was developed for the transition state. The effectiveness of the proposed approach was validated using a self-developed air cushion furnace experimental platform. This study has important value for the process prediction and control of air cushion furnaces.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1820-1824, 2019 Dec.
Article in Chinese | MEDLINE | ID: mdl-31839044

ABSTRACT

OBJECTIVE: To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). METHODS: The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. RESULTS: All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. CONCLUSION: allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , DNA (Cytosine-5-)-Methyltransferases , DNA Methyltransferase 3A , Humans , Mutation , Retrospective Studies , Transplantation Conditioning , fms-Like Tyrosine Kinase 3
20.
PLoS Genet ; 15(8): e1008331, 2019 08.
Article in English | MEDLINE | ID: mdl-31412019

ABSTRACT

Holometabolous insects stop feeding at the final larval instar stage and then undergo metamorphosis; however, the mechanism is unclear. In the present study, using the serious lepidopteran agricultural pest Helicoverpa armigera as a model, we revealed that 20-hydroxyecdysone (20E) binds to the dopamine receptor (DopEcR), a G protein-coupled receptor, to stop larval feeding and promote pupation. DopEcR was expressed in various tissues and its level increased during metamorphic molting under 20E regulation. The 20E titer was low during larval feeding stages and high during wandering stages. By contrast, the dopamine (DA) titer was high during larval feeding stages and low during the wandering stages. Injection of 20E or blocking dopamine receptors using the inhibitor flupentixol decreased larval food consumption and body weight. Knockdown of DopEcR repressed larval feeding, growth, and pupation. 20E, via DopEcR, promoted apoptosis; and DA, via DopEcR, induced cell proliferation. 20E opposed DA function by repressing DA-induced cell proliferation and AKT phosphorylation. 20E, via DopEcR, induced gene expression and a rapid increase in intracellular calcium ions and cAMP. 20E induced the interaction of DopEcR with G proteins αs and αq. 20E, via DopEcR, induced protein phosphorylation and binding of the EcRB1-USP1 transcription complex to the ecdysone response element. DopEcR could bind 20E inside the cell membrane or after being isolated from the cell membrane. Mutation of DopEcR decreased 20E binding levels and related cellular responses. 20E competed with DA to bind to DopEcR. The results of the present study suggested that 20E, via binding to DopEcR, arrests larval feeding and promotes pupation.


Subject(s)
Ecdysterone/metabolism , Insect Proteins/metabolism , Moths/physiology , Receptors, Dopamine/metabolism , Animals , Dopamine/metabolism , Dopamine Antagonists/pharmacology , Feeding Behavior/drug effects , Feeding Behavior/physiology , Flupenthixol/pharmacology , Gene Knockdown Techniques , Insect Proteins/genetics , Larva/drug effects , Larva/physiology , Molting/drug effects , Molting/physiology , Moths/drug effects , RNA Interference , Receptors, Dopamine/genetics , Sf9 Cells
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