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1.
J Colloid Interface Sci ; 669: 787-793, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38744156

ABSTRACT

Developing highly efficient and sustainable hydrogen evolution reaction (HER) electrocatalysts is important for the practical application of emerging energy technologies. The spherical structure and phosphorus-rich properties of Chlorella can facilitate the construction of comparable transition metal phosphide electrocatalysts. Here, a microorganism template strategy is proposed to construct a cobalt-phosphide-graphene hybrid. Chlorella can absorb metal ions, and the generated rough spherical nanoparticles are uniformly distributed around the reduced graphene oxide nanosheets. This designed catalyst has comparable HER performance in acidic electrolytes and needs an overpotential of only 153 mV at a current density of 10 mA cm-2. The experimental and density functional theory results imply that the charge redistribution between Co2P and pyrrole-N is the key factor in enhancing the HER activity. The induced electron aggregation at the N and P sites can serve as a key active site for absorbing the adsorbed hydrogen atom intermediate to accelerate the HER process, contributing to the active sites of Co2P- and pyrrole-N-doped carbon with 0 eV hydrogen adsorption free energy. This work provides a broad idea for synthesizing advanced catalysts by a biological template approach, facilitating the innovative integration of biology and emerging electrochemical energy technologies.

2.
Angew Chem Int Ed Engl ; : e202404703, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38655625

ABSTRACT

Self-assembly in living cells represents one versatile strategy for drug delivery; however, it suffers from the limited precision and efficiency. Inspired by viral traits, we here report a cascade targeting-hydrolysis-transformation (THT) assembly of glycosylated peptides in living cells holistically resembling viral infection for efficient cargo delivery and combined tumor therapy. We design a glycosylated peptide via incorporating a ß-galactose-serine residue into bola-amphiphilic sequences. Co-assembling of the glycosylated peptide with two counterparts containing irinotecan (IRI) or ligand TSFAEYWNLLSP (PMI) results in formation of the glycosylated co-assemblies SgVEIP, which target cancer cells via ß-galactose-galectin-1 association and undergo galactosidase-induced morphological transformation. While GSH-reduction causes release of IRI from the co-assemblies, the PMI moieties release p53 and facilitate cell death via binding with protein MDM2. Cellular experiments show membrane targeting, endo-/lysosome-mediated internalization and in situ formation of nanofibers in cytoplasm by SgVEIP. This cascade THT process enables efficient delivery of IRI and PMI into cancer cells secreting Gal-1 and overexpressing ß-galactosidase. In vivo studies illustrate enhanced tumor accumulation and retention of the glycosylated co-assemblies, thereby suppressing tumor growth. Our findings demonstrate an in situ assembly strategy mimicking viral infection, thus providing a new route for drug delivery and cancer therapy in the future.

3.
Hum Exp Toxicol ; 43: 9603271231218707, 2024.
Article in English | MEDLINE | ID: mdl-38487884

ABSTRACT

BACKGROUND: Bupivacaine (BUP), a long-acting local anesthetic, has been widely used in analgesia and anesthesia. However, evidence strongly suggests that excessive application of BUP may lead to neurotoxicity in neurons. Sphingosine kinase 2 (SPHK2) has been reported to exert neuroprotective effects. In this study, we intended to investigate the potential role and mechanism of SPHK2 in BUP-induced neurotoxicity in dorsal root ganglion (DRG) neurons. METHODS: DRG neurons were cultured with BUP to simulate BUP-induced neurotoxicity in vitro. CCK-8, LDH, and flow cytometry assays were performed to detect the viability, LDH activity, and apoptosis of DRG neurons. RT-qPCR and western blotting was applied to measure gene and protein expression. Levels. MeRIP-qPCR was applied for quantification of m6A modification. RIP-qPCR was used to analyze the interaction between SPHK2 and YTHDF1. RESULTS: SPHK2 expression significantly declined in DRG neurons upon exposure to BUP. BUP challenge substantially reduced the cell viability and increased the apoptosis rate in DRG neurons, which was partly abolished by SPHK2 upregulation. YTHDF1, an N6-methyladenosine (m6A) reader, promoted SPHK2 expression in BUP-treated DRG neurons in an m6A-dependent manner. YTHDF1 knockdown partly eliminated the increase in SPHK2 protein level and the protection against BUP-triggered neurotoxicity in DRG neurons mediated by SPHK2 overexpression. Moreover, SPHK2 activated the PI3K/AKT signaling to protect against BUP-induced cytotoxic effects on DRG neurons. CONCLUSIONS: In sum, YTHDF1-mediated SPHK2 upregulation ameliorated BUP-induced neurotoxicity in DRG neurons via promoting activation of the PI3K/AKT signaling pathway.


Subject(s)
Bupivacaine , Neurotoxicity Syndromes , Phosphotransferases (Alcohol Group Acceptor) , Humans , Bupivacaine/toxicity , Up-Regulation , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Neurotoxicity Syndromes/prevention & control , Apoptosis , RNA-Binding Proteins
4.
Commun Biol ; 7(1): 215, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383737

ABSTRACT

Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.


Subject(s)
Adenine , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Adenine/analogs & derivatives , Autophagy/genetics , Carcinoma, Non-Small-Cell Lung/pathology , CD47 Antigen/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Intracellular Signaling Peptides and Proteins , Lung Neoplasms/pathology , Macrophages/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Phagocytosis , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
5.
J Phys Chem Lett ; 15(4): 1070-1078, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38261575

ABSTRACT

Two-dimensional (2D) metal borides (MBenes) with unique electronic structures and physicochemical properties hold great promise for various applications. Given the abundance of boron clusters, we proposed employing them as structural motifs to design 2D transition metal boron cluster compounds (MBnenes), an extension of MBenes. Herein, we have designed three stable MBnenes (M4(B12)2, M = Mn, Fe, Co) based on B12 clusters and investigated their electronic and magnetic properties using first-principles calculations. Mn4(B12)2 and Co4(B12)2 are semiconductors, while Fe4(B12)2 exhibits metallic behavior. The unique structure in MBnenes allows the coexistence of direct exchange interactions between adjacent metal atoms and indirect exchange interactions mediated by the clusters, endowing them with a Néel temperature (TN) up to 772 K. Moreover, both Mn4(B12)2 and Fe4(B12)2 showcase strain-independent room-temperature magnetism, making them potential candidates for spintronics applications. The MBnenes family provides a fresh avenue for the design of 2D materials featuring unique structures and excellent physicochemical properties.

6.
ACS Med Chem Lett ; 14(6): 737-745, 2023 Jun 08.
Article in English | MEDLINE | ID: mdl-37312858

ABSTRACT

Antibiotic overuse has caused the increasingly serious problem of bacterial drug resistance, with numerous marketed antibiotics exhibiting significantly reduced activity against drug-resistant bacteria. Therefore, there is urgent demand for the development of novel antibiotics. Pleuromutilin is a tricyclic diterpene exhibiting antibacterial activity against Gram-positive bacteria and is currently considered the most promising natural antibiotic. In this study, novel pleuromutilin derivatives were designed and synthesized by introducing thioguanine units, and their antibacterial activities against drug-resistant strains were evaluated in vitro and in vivo. Compound 6j was observed to have a rapid bactericidal effect, low cytotoxicity, and potent antibacterial activity. The in vitro results suggest that 6j has a significant therapeutic effect on local infections, and its activity is equal to that of retapamulin, an anti-Staphylococcus aureus pleuromutilin derivative.

7.
J Vasc Surg ; 78(2): 430-437.e4, 2023 08.
Article in English | MEDLINE | ID: mdl-37076105

ABSTRACT

OBJECTIVE: Carotid artery stenting (CAS) has become an alternative strategy to carotid endarterectomy for carotid artery stenosis. Residual stenosis was an independent risk factor for restenosis, with the latter affecting the long-term outcomes of CAS. This multicenter study aimed to evaluate the echogenicity of plaques and hemodynamic alteration by color duplex ultrasound (CDU) examination and investigate their effects on the residual stenosis after CAS. METHODS: From June 2018 to June 2020, 454 patients (386 males and 68 females) with a mean age of 67.2 ± 7.9 years, who underwent CAS from 11 advanced stroke centers in China were enrolled. One week before recanalization, CDU was used to evaluate the responsible plaques, including the morphology (regular or irregular), echogenicity of the plaques (iso-, hypo-, or hyperechoic) and calcification characteristics (without calcification, superficial calcification, inner calcification, and basal calcification). One week after CAS, the alteration of diameter and hemodynamic parameters were evaluated by CDU, and the occurrence and degree of residual stenosis were determined. In addition, magnetic resonance imaging was performed before and during the 30-day postprocedural period to identify new ischemic cerebral lesions. RESULTS: The rate of composite complications, including cerebral hemorrhage, symptomatic new ischemic cerebral lesions, and death after CAS, was 1.54% (7/454 cases). The rate of residual stenosis after CAS was 16.3% (74/454 cases). After CAS, both the diameter and peak systolic velocity (PSV) improved in the preprocedural 50% to 69% and 70% to 99% stenosis groups (P < .05). Compared with the groups without residual stenosis and with <50% residual stenosis, the PSV of all three segments of stent in the 50% to 69% residual stenosis group were the highest, and the difference in the midsegment of stent PSV was the largest (P < .05). Logistic regression analysis showed that preprocedural severe (70% to 99%) stenosis (odds ratio [OR], 9.421; P = .032), hyperechoic plaques (OR, 3.060; P = .006) and plaques with basal calcification (OR, 1.885; P = .049) were independent risk factors for residual stenosis after CAS. CONCLUSIONS: Patients with hyperechoic and calcified plaques of the carotid stenosis are at a high risk of residual stenosis after CAS. CDU is an optimal, simple and noninvasive imaging method to evaluate plaque echogenicity and hemodynamic alterations during the perioperative period of CAS, which can help surgeons to select the optimal strategies and prevent the occurrence of residual stenosis.


Subject(s)
Carotid Stenosis , Endarterectomy, Carotid , Plaque, Atherosclerotic , Stroke , Male , Female , Humans , Middle Aged , Aged , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/therapy , Constriction, Pathologic/etiology , Stents/adverse effects , Endarterectomy, Carotid/adverse effects , Stroke/epidemiology , Plaque, Atherosclerotic/complications , Carotid Arteries/surgery , Hemodynamics , Treatment Outcome
8.
Int J Mol Sci ; 25(1)2023 Dec 23.
Article in English | MEDLINE | ID: mdl-38203421

ABSTRACT

Anthurium andraeanum is a tropical ornamental flower. The cost of Anthurium production is higher under low temperature (non-freezing) conditions; therefore, it is important to increase its cold tolerance. However, the molecular mechanisms underlying the response of Anthurium to cold stress remain elusive. In this study, comparative physiological and transcriptome sequencing analyses of two cultivars with contrasting cold tolerances were conducted to evaluate the cold stress response at the flowering stage. The activities of superoxide dismutase and peroxidase and the contents of proline, soluble sugar, and malondialdehyde increased under cold stress in the leaves of the cold tolerant cultivar Elegang (E) and cold susceptible cultivar Menghuang (MH), while the soluble protein content decreased in MH and increased in E. Using RNA sequencing, 24,695 differentially expressed genes (DEGs) were identified from comparisons between cultivars under the same conditions or between the treatment and control groups of a single cultivar, 9132 of which were common cold-responsive DEGs. Heat-shock proteins and pectinesterases were upregulated in E and downregulated in MH, indicating that these proteins are essential for Anthurium cold tolerance. Furthermore, four modules related to cold treatment were obtained by weighted gene co-expression network analysis. The expression of the top 20 hub genes in these modules was induced by cold stress in E or MH, suggesting they might be crucial contributors to cold tolerance. DEGs were significantly enriched in plant hormone signal transduction pathways, trehalose metabolism, and ribosomal proteins, suggesting these processes play important roles in Anthurium's cold stress response. This study provides a basis for elucidating the mechanism of cold tolerance in A. andraeanum and potential targets for molecular breeding.


Subject(s)
Araceae , Common Cold , Cold Temperature , Araceae/genetics , Cold-Shock Response/genetics , Gene Expression Profiling
9.
Front Med (Lausanne) ; 9: 1017074, 2022.
Article in English | MEDLINE | ID: mdl-36388879

ABSTRACT

Parvimonas micra is an anaerobic Gram-positive coccus frequently found in the oral cavity and gastrointestinal tract, but rarely in the lung. Therefore, pneumonia caused by P. micra is also rare. Although there are some reports of P. micra related pneumonia due to aspiration or blood-borne infection with definite remote infection source, there are no reported cases of hematogenous P. micra pneumonia in healthy adults lacking a remote source of infection. Herein, we described the intact disease of P. micra-related pneumonia mimicking hematogenous Staphylococcus aureus pneumonia in terms of chest imagery and diagnosed via metagenomic next-generation sequencing (mNGS). Interestingly, there was no clear remote pathogenic source identified in the patient. Microbiome analysis revealed dysbiosis of the oral flora possibly related to poor oral hygiene and a long history of smoking. The patient was treated with moxifloxacin for 3 months. Ultimately, computed tomography (CT) of the chest showed total resolution of the lung lesion. Clinicians need to update the etiology of community-acquired pneumonia. When antibiotic therapy is not effective, pathogen examination becomes very important. New methods of pathogen detection such as mNGS should be employed to this end. For the treatment of P. micra pneumonia, no standardized course of treatment was reported. Imaging absorption of lung infections may provide a more objective guidance for the duration of antibiotics in P. micra pneumonia.

10.
Child Abuse Negl ; 134: 105931, 2022 12.
Article in English | MEDLINE | ID: mdl-36302286

ABSTRACT

BACKGROUND: Maternal personal history of childhood abuse has been found to predict child social-emotional problems; however, little is known about the intergenerational associations between maternal childhood abuse and child cognitive outcomes. OBJECTIVE: This study aims at examining the intergenerational associations of maternal childhood emotional abuse and physical abuse with child executive functions among Chinese families with preschoolers, and exploring how these associations are mediated by maternal perspective-taking skills and mother-child conflict. METHODS: Participants were 309 preschoolers (152 boys) aged 2-6 years and their mothers. Mothers reported on their childhood abuse histories, perspective taking, and mother-child conflict at baseline (T1). Five months later (T2), child executive functions including working memory, inhibitory control, and cognitive flexibility were assessed using five computerized tasks. RESULTS: After controlling for child gender and age, associations with child executive functions were found for maternal childhood emotional abuse, but not physical abuse. Specifically, severer childhood emotional abuse directly predicted lower levels of child cognitive flexibility. Furthermore, chained mediation paths were found from maternal childhood emotional abuse to lower levels of child working memory and inhibitory control through worse maternal perspective taking skills and then more mother-child conflicts. CONCLUSIONS: Our findings provide evidence for less optimal executive functions among preschoolers with emotionally abused mothers. Developing strategies to resolve the long-lasting impacts of maternal childhood emotional abuse may be important for reducing the risks of being unable to fully achieve the cognitive potentials of the next generation.


Subject(s)
Child Abuse , Mother-Child Relations , Male , Female , Child, Preschool , Child , Humans , Mother-Child Relations/psychology , Executive Function , Mothers/psychology , Child Abuse/psychology , China/epidemiology
11.
Int J Mol Sci ; 23(11)2022 May 30.
Article in English | MEDLINE | ID: mdl-35682805

ABSTRACT

Salt cress (Eutrema salsugineum, aka Thellungiella salsuginea) is an extremophile and a close relative of Arabidopsis thaliana. To understand the mechanism of selection of complex traits under natural variation, we analyzed the physiological and proteomic differences between Shandong (SD) and Xinjiang (XJ) ecotypes. The SD ecotype has dark green leaves, short and flat leaves, and more conspicuous taproots, and the XJ ecotype had greater biomass and showed clear signs of senescence or leaf shedding with age. After 2-DE separation and ESI-MS/MS identification, between 25 and 28 differentially expressed protein spots were identified in shoots and roots, respectively. The proteins identified in shoots are mainly involved in cellular metabolic processes, stress responses, responses to abiotic stimuli, and aging responses, while those identified in roots are mainly involved in small-molecule metabolic processes, oxidation-reduction processes, and responses to abiotic stimuli. Our data revealed the evolutionary differences at the protein level between these two ecotypes. Namely, in the evolution of salt tolerance, the SD ecotype highly expressed some stress-related proteins to structurally adapt to the high salt environment in the Yellow River Delta, whereas the XJ ecotype utilizes the specialized energy metabolism to support this evolution of the short-lived xerophytes in the Xinjiang region.


Subject(s)
Arabidopsis , Brassicaceae , Arabidopsis/metabolism , Brassicaceae/metabolism , Ecotype , Gene Expression Regulation, Plant , Proteomics , Stress, Physiological , Tandem Mass Spectrometry
12.
J Am Chem Soc ; 144(21): 9312-9323, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35587998

ABSTRACT

Self-sorting is a common phenomenon in eukaryotic cells and represents one of the versatile strategies for the formation of advanced functional materials; however, developing artificial self-sorting assemblies within living cells remains challenging. Here, we report on the GSH-responsive in situ self-sorting peptide assemblies within cancer cells for simultaneous organelle targeting to promote combinatorial organelle dysfunction and thereby cell death. The self-sorting system was created via the design of two peptides E3C16E6 and EVMSeO derived from lipid-inspired peptide interdigitating amphiphiles and peptide bola-amphiphiles, respectively. The distinct organization patterns of the two peptides facilitate their GSH-induced self-sorting into isolated nanofibrils as a result of cleavage of disulfide-connected hydrophilic domains or reduction of selenoxide groups. The GSH-responsive in situ self-sorting in the peptide assemblies within HeLa cells was directly characterized by super-resolution structured illumination microscopy. Incorporation of the thiol and ER-targeting groups into the self-sorted assemblies endows their simultaneous targeting of endoplasmic reticulum and Golgi apparatus, thus leading to combinatorial organelle dysfunction and cell death. Our results demonstrate the establishment of the in situ self-sorting peptide assemblies within living cells, thus providing a unique platform for drug targeting delivery and an alternative strategy for modulating biological processes in the future.


Subject(s)
Golgi Apparatus , Peptides , Endoplasmic Reticulum/metabolism , Golgi Apparatus/metabolism , HeLa Cells , Humans , Peptides/chemistry , Protein Transport
13.
Contrast Media Mol Imaging ; 2021: 8997105, 2021.
Article in English | MEDLINE | ID: mdl-34867117

ABSTRACT

This work aimed to explore the analysis and diagnosis of children with tic disorder by magnetic resonance imaging (MRI) features under convolutional neural network (CNN), to provide a certain reference basis for clinical identification. A total of 45 children diagnosed with tic disorder in hospital from January 2018 to June 2020 were selected as the research subjects. A total of 30 normal children were selected as the control group. MRI images were collected, and CNN was constructed for image processing. The results showed that the convolutional neural network could significantly improve the speed of MRI reconstruction and can improve the diagnostic accuracy. Compared with normal children, the metabolites in children with tic disorder were slightly increased, but there was no statistical significance (P > 0.05). The results of the Yale score showed that the proportion of children with moderate illness was significantly greater than that of children with mild and severe illness. In short, the pathological changes of tic disorder were effectively discovered by MRI based on CNN algorithms, which can provide a reference for clinical identification.


Subject(s)
Neural Networks, Computer , Tic Disorders , Algorithms , Child , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Tic Disorders/diagnostic imaging
14.
J Enzyme Inhib Med Chem ; 36(1): 764-775, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33733986

ABSTRACT

Antibiotics resistance is becoming increasingly common, involving almost all antibiotics on the market. Diseases caused by drug resistant bacteria, such as MRSA, have high mortality and negatively affect public health. The development of new drugs would be an effective means of solving this problem. Modifications based on bioactive natural products could greatly shorten drug development time and improve success rate. Pleuromutilin, a natural product from the basidiomycete bacterial species, is a promising antibiotic candidate. In this study, a series of novel pleuromutilin derivatives possessing piperazinyl urea linkage were efficiently synthesised, and their antibacterial activities and bactericidal properties were evaluated via MIC, MBC and Time-kill kinetics assays. The results showed that all compounds exhibited potent activities against tested strains, especially MRSA strains with MIC values as low as 0.125 µg/mL; 8 times lower than that of marketed antibiotic Tiamulin. Docking studies indicate substituted piperazinyl urea derivatives could provide hydrogen bonds and initiate π-π stacking between molecules and surrounding residues.


Subject(s)
Anti-Bacterial Agents/pharmacology , Diterpenes/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Molecular Docking Simulation , Polycyclic Compounds/pharmacology , Urea/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Diterpenes/chemical synthesis , Diterpenes/chemistry , HEK293 Cells , Humans , Microbial Sensitivity Tests , Molecular Structure , Polycyclic Compounds/chemical synthesis , Polycyclic Compounds/chemistry , Urea/analogs & derivatives , Urea/chemistry , Pleuromutilins
15.
Plant Signal Behav ; 16(3): 1862565, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33404284

ABSTRACT

Gamma-aminobutyric acid (GABA) is a ubiquitous four-carbon, non-protein amino acid. GABA has been widely studied in animal central nervous systems, where it acts as an inhibitory neurotransmitter. In plants, it is metabolized through the GABA shunt pathway, a bypass of the tricarboxylic acid (TCA) cycle. Additionally, it can be synthesized through the polyamine metabolic pathway. GABA acts as a signal in Agrobacterium tumefaciens-mediated plant gene transformation and in plant development, especially in pollen tube elongation (to enter the ovule), root growth, fruit ripening, and seed germination. It is accumulated during plant responses to environmental stresses and pathogen and insect attacks. A high concentration of GABA elevates plant stress tolerance by improving photosynthesis, inhibiting reactive oxygen species (ROS) generation, activating antioxidant enzymes, and regulating stomatal opening in drought stress. The transporters of GABA in plants are reviewed in this work. We summarize the recent research on GABA function and transporters with the goal of providing a review of GABA in plants.


Subject(s)
Plants/metabolism , gamma-Aminobutyric Acid/metabolism , GABA Plasma Membrane Transport Proteins/metabolism , Metabolic Networks and Pathways , Signal Transduction , Stress, Physiological
16.
J Biochem Mol Toxicol ; 35(1): e22620, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32886829

ABSTRACT

Numerous evidence link aberrant nuclear ß-catenin accumulation to the development of breast cancer resistance, therefore, targeted inhibition of ß-catenin nuclear translocation may effectively improve the chemosensitivity of breast cancer. Doxorubicin (Dox) is the most commonly used chemotherapeutic drug for breast cancer. Here, we determined that tanshinone II A (Tan II A) could improve the sensitivity of Dox-resistant breast cancer MCF-7/dox cells to Dox, and evaluated whether the sensitization effect of Tan II A on Dox was targeted to inhibit ß-catenin nuclear translocation. The results showed that Tan II A not only significantly inhibited the nuclear translocation of ß-catenin in MCF-7/dox cells treated by Dox but also inhibited the nuclear translocation of ß-catenin in MCF-7 cells treated by Dox to a certain degree. Furthermore, when the above two cells treated by Dox combined with Tan II A were intervened with ß-catenin agonist WAY-262611, with the re-nuclear translocation of ß-catenin in the cells, the sensitization effect of Tan II A on Dox was greatly reduced. These results indicated that Tan II A could improve the chemosensitivity of breast cancer cells to Dox by inhibiting ß-catenin nuclear translocation. Therefore, Tan II A could be used as a potential chemosensitizer in combination with Dox for breast cancer chemotherapy.


Subject(s)
Benzofurans/pharmacology , Breast Neoplasms , Cell Nucleus/metabolism , Drug Resistance, Neoplasm/drug effects , Neoplasm Proteins/metabolism , beta Catenin/metabolism , Active Transport, Cell Nucleus/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Nucleus/pathology , Female , Humans , MCF-7 Cells
17.
Microb Pathog ; 153: 104594, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33157218

ABSTRACT

As a multifactor disease, the bovine respiratory disease complex (BRDC) causes high morbidity and mortality that is devastating to the cattle industry. To assess viral infections in beef cattle suffering from respiratory diseases in Inner Mongolia, 302 nasal swabs and serum samples were randomly collected from cattle with mild respiratory symptoms between March 2018 and May 2019. Our results showed that the rate of RT-PCR results positive for nucleic acids of viral pathogens in 6 cities was between 54 and 80%.The rates of bovine viral diarrhea virus (BVDV), bovine herpesvirus 1 (BHV-1), bovine parainfluenza virus type 3(BPIV3), and bovine respiratory syncytial virus(BRSV)infections were 44.70% (135/302), 24.83% (75/302), 5.63% (17/302), and 6.95% (21/302),respectively. There are also 8.94% (27/302) of samples were positive for BVDV and BHV-1, and 3.97% (12/302) of samples were positive for BPIV3 and BRSV. In addition, the RT-PCR products were sequenced, and phylogenetic analysis based on these sequences was performed. The results indicated that: a) all of the BVDV isolates were BVDV-1 and were classified as BVDV-1a (66.67%) and BVDV-1b (33.33%); b) all of the BHV-1 isolates were classified as subtype 1.1; 44.44% of the isolates were closely related to modified live viral vaccine strains, and 55.56% of the isolates were closer to epidemic strains; c) all of the BPIV3 isolates belonged to BPIV3c; d) all of the BRSV isolates were classified into subgroup III. It is suggested that an important cause of respiratory diseases for beef cattle is viral infection, and phylogenetic analysis can help us choose the proper strain to develop a vaccine.


Subject(s)
Bovine Respiratory Disease Complex , Cattle Diseases , Diarrhea Virus 1, Bovine Viral , Respiratory Syncytial Virus, Bovine , Animals , Bovine Respiratory Disease Complex/epidemiology , Cattle , Cattle Diseases/epidemiology , China/epidemiology , Phylogeny , Respiratory Syncytial Virus, Bovine/genetics
18.
BMC Plant Biol ; 20(1): 547, 2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33287712

ABSTRACT

BACKGROUND: Organ shape and size covariation (allometry) factors are essential concepts for the study of evolution and development. Although ample research has been conducted on organ shape and size, little research has considered the correlated variation of these two traits and quantitatively measured the variation in a common framework. The genetic basis of allometry variation in a single organ or among different organs is also relatively unknown. RESULTS: A principal component analysis (PCA) of organ landmarks and outlines was conducted and used to quantitatively capture shape and size variation in leaves and petals of multiparent advanced generation intercross (MAGIC) populations of Arabidopsis thaliana. The PCA indicated that size variation was a major component of allometry variation and revealed negatively correlated changes in leaf and petal size. After quantitative trait loci (QTL) mapping, five QTLs for the fourth leaf, 11 QTLs for the seventh leaf, and 12 QTLs for petal size and shape were identified. These QTLs were not identical to those previously identified, with the exception of the ER locus. The allometry model was also used to measure the leaf and petal allometry covariation to investigate the evolution and genetic coordination between homologous organs. In total, 12 QTLs were identified in association with the fourth leaf and petal allometry covariation, and eight QTLs were identified to be associated with the seventh leaf and petal allometry covariation. In these QTL confidence regions, there were important genes associated with cell proliferation and expansion with alleles unique to the maximal effects accession. In addition, the QTLs associated with life-history traits, such as days to bolting, stem length, and rosette leaf number, which were highly coordinated with climate change and local adaption, were QTL mapped and showed an overlap with leaf and petal allometry, which explained the genetic basis for their correlation. CONCLUSIONS: This study explored the genetic basis for leaf and petal allometry and their interaction, which may provide important information for investigating the correlated variation and evolution of organ shape and size in Arabidopsis.


Subject(s)
Arabidopsis/genetics , Flowers/genetics , Gene Expression Regulation, Plant , Genetic Variation , Plant Leaves/genetics , Quantitative Trait Loci/genetics , Alleles , Arabidopsis/anatomy & histology , Chromosome Mapping , Chromosomes, Plant/genetics , Flowers/anatomy & histology , Genes, Plant/genetics , Phenotype , Plant Leaves/anatomy & histology , Principal Component Analysis
19.
Chem Commun (Camb) ; 56(69): 10046-10049, 2020 Sep 07.
Article in English | MEDLINE | ID: mdl-32729584

ABSTRACT

Highly transparent and active Pt-Mo2C counter electrodes were successfully fabricated by the strong metal-support interaction, with high dispersity of Pt nanoclusters on Mo2C support, which endowed bifacial dye-sensitized solar cells with a rear-to-front efficiency ratio as high as 0.75.

20.
Mol Med Rep ; 22(3): 1839-1846, 2020 09.
Article in English | MEDLINE | ID: mdl-32582982

ABSTRACT

Although the cardiovascular pharmacological actions of Tanshinone IIA (TanIIA) have been extensively studied, research on its roles in cardiac regeneration is still insufficient. The present study employed the cardiac myoblast cell line H9c2 to evaluate the possible roles of TanIIA in cardiac regeneration. It was found that certain concentration of TanIIA inhibited cell proliferation by suppressing the expression of proteins related to the cell cycle [cyclin dependent kinase (CDK)4, CDK6 and cyclin D1] and proliferation [c­Myc, octamer­binding transcription factor 4 (Oct4) and proliferating cell nuclear antigen (PCNA)] without inducing apoptosis. In this process, the expression of cardiac troponin in the treated cells was significantly increased and the migration of the treated cells toward the wound area was significantly enhanced. Meanwhile, TanIIA inhibited the canonical signaling pathway through increasing the expression of glycogen synthase kinase 3ß (GSK­3ß) and adenomatous polyposis coli (APC) and increased the expression of Wnt11 and Wnt5a in the noncanonical Wnt signaling pathway. Following ß­catenin agonist WAY­262611 intervention, the effect of TanIIA on the promotion of cardiac differentiation and improved cell migration was significantly reduced. In conclusion, it was hypothesized that TanIIA could promote cardiac differentiation and improve cell motility by modulating the Wnt/ß­catenin signaling pathway. These results suggest that TanIIA may play beneficial roles in myocardial regeneration following stem cell transplantation.


Subject(s)
Abietanes/pharmacology , Myocytes, Cardiac/cytology , Wnt Signaling Pathway/drug effects , Animals , Cell Differentiation/drug effects , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Cyclin D1/metabolism , Cyclin-Dependent Kinase 4/metabolism , Cyclin-Dependent Kinase 6/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Rats
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