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1.
Environ Pollut ; 292(Pt A): 118368, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656676

RESUMO

As one of the predominant compositions of PM2.5 (particulate matter with aerodynamic diameter ≤2.5 µm), carbonaceous aerosols not only have adverse effects on air quality, but also can affect climate change. Although there are extensive recent studies on carbonaceous aerosols, comprehensive studies on their socioeconomic influencing factors in a resource-based city are relatively limited. In this study, the spatial-temporal variations of organic carbon (OC), elemental carbon (EC), and secondary organic carbon (SOC) were investigated in January, July, and October in 2015 and April in 2016 in Wuhai and its surrounding areas. The population distribution and industry layout have led to the uneven spatial-temporal distribution of carbonaceous aerosols. The concentrations of carbonaceous aerosols were higher in winter due to the unfavorable meteorology and the increased emissions from heating. The SOC is a significant contributor to OC in the cold season (52.0% for January). Primary carbonaceous aerosols pollution is higher in the industrial sites of resource-based cities, whereas the SOC makes a significant contribution in the residential sites. The results of backward-trajectory and concentration-weighted trajectory analysis suggest that the local emissions and short-range atmospheric transport from nearby areas have a significant impact on PM2.5 and carbonaceous aerosols. A strong correlation between population density and OC/EC ratio was found, indicating that the megacities with high population density have a higher SOC contribution than the resource-based cities. Resource-based cities are characterized by high level of primary OC emissions, whereas cities with high energy efficiency have a more significant SOC contribution. These results provide a more comprehensive understanding of carbonaceous aerosols in a resource-based city.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , Carbono/análise , China , Cidades , Conservação de Recursos Energéticos , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/análise , Densidade Demográfica , Estações do Ano
2.
Virology ; 565: 58-64, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34739917

RESUMO

Porcine Epidemic Diarrhea (PED) is a highly contagious intestinal disease which mostly caused by Porcine Epidemic Diarrhea Virus (PEDV). The PED has caused huge economic losses to the pig industry all over the world and a valid PEDV vaccine is needed to prevent the infection. In this study, we constructed expression plasmid based on the spike (S) gene of the epidemic PEDV strain. The recombinant eukaryotic S (Se) and prokaryotic S (Sp) subunit proteins were expressed and purified as vaccine antigens. We designed a new subunit vaccine based on S proteins, adjuvanted with layered double hydroxide (LDH). The results indicated that the LDH adjuvanted subunit vaccines induced a better immune effect in terms of antibody level and cellular immune response. In conclusion, this study showed a new design of a PEDV subunit vaccine with nanotechnology and demonstrated the potential for its clinical application.

3.
Phytochem Anal ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34755399

RESUMO

INTRODUCTION: In addition to the mycotoxin swainsonine, the locoweed endophytic fungus Alternaria oxytropis (Pleosporaceae) also produces a series of rarely reported, highly oxygenated bicyclic guaiane sesquiterpenoids. Few investigations on the electrospray tandem mass fragmentation pattern of this sesquiterpenoid have been reported. OBJECTIVES: We aimed to analyze and detect new guaiane sesquiterpenoid analogues from crude extracts of the locoweed endophytic fungus A. oxytropis by UPLC-Q-TOF-MS/MS experiments. MATERIALS AND METHODS: Oxytropiols A-J (1-10) and the extract of the locoweed endophytic fungus A. oxytropis were analyzed by UPLC-Q-TOF-MS/MS in positive mode. RESULTS: Typical neutral losses, McLafferty rearrangement, 1,2-rearrangement, and 1,3-rearrangement were considered to be the main fragmentation patterns for the [M + H]+ /[M + Na]+ ions of 1-10 by UPLC-Q-TOF-MS/MS experiments, and possible fragmentation pathways of 1-10 were suggested. A unique and undescribed analogue named oxytropiol K (11) was found in the extract based on UPLC-Q-TOF-MS/MS analysis. Compound 11 was isolated and elucidated by NMR spectrometry, and its UPLC-Q-TOF-MS/MS analysis was consistent with the fragmentation pathways of 1-10. CONCLUSION: The results further support that UPLC-Q-TOF-MS/MS is a powerful and sensitive tool for the characterization of known compounds (dereplication) and the detection of new analogues from crude extracts and imply that the locoweed endophytic fungus A. oxytropis, with few chemical investigations, is an important resource for undescribed metabolites.

4.
BMC Pulm Med ; 21(1): 367, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34775948

RESUMO

BACKGROUND: Hypoxemia frequently occurs during bronchoscopy. High-flow nasal cannula (HFNC) oxygen therapy may be a feasible alternative to prevent the deterioration of gas exchange during bronchoscopy. With the convenience of clinical use in mind, we modified an HFNC using a single cannula. This clinical trial was designed to test the hypothesis that a modified HFNC would decrease the proportion of patients with a single moment of peripheral arterial oxygen saturation (SpO2) < 90% during bronchoscopy. METHODS: In this single-center, prospective randomized controlled trial, hospitalized patients in the respiratory department in need of diagnostic bronchoscopy were randomly assigned to a modified HFNC oxygen therapy group or a conventional oxygen therapy (COT) group. The primary outcome was the proportion of patients with a single moment of SpO2 < 90% during bronchoscopy. RESULTS: Eight hundred and twelve patients were randomized to the modified HFNC (n = 406) or COT (n = 406) group. Twenty-four patients were unable to cooperate or comply with bronchoscopy. Thus, 788 patients were included in the analysis. The proportion of patients with a single moment of SpO2 < 90% during bronchoscopy in the modified HFNC group was significantly lower than that in the COT group (12.5% vs. 28.8%, p < 0.001). There were no significant differences in the fraction of inspired oxygen between the two groups. The lowest SpO2 during bronchoscopy and 5 min after bronchoscopy in the modified HFNC group was significantly higher than that in the COT group. Multivariate analysis showed that a baseline forced vital capacity (FVC) < 2.7 L (OR, 0.276; 95% CI, 0.083-0.919, p = 0.036) and a volume of fluid instilled > 60 ml (OR, 1.034; 95% CI, 1.002-1.067, p = 0.036) were independent risk factors for hypoxemia during bronchoscopy in the modified HFNC group. CONCLUSIONS: A modified HFNC could decrease the proportion of patients with a single moment of SpO2 < 90% during bronchoscopy. A lower baseline FVC and large-volume bronchoalveolar lavage may predict desaturation during bronchoscopy when using a modified HFNC. Trial registration ClinicalTrials. Gov: NCT02606188. Registered 17 November 2015.

5.
Phytochemistry ; 194: 112996, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34844037

RESUMO

Nine undescribed compounds, including six tremulane-type sesquiterpenoids, irpexolaceus A-F, one phenolic bisabolane-type sesquiterpenoid, irpexolaceus G, and two furan derivatives, irpexonjust A-B, as well as eight known analogs, were isolated from an endophytic fungus (Irpex lacteus OV38) of Orychophragmus violaceus (L.) O.E. Schulz, a Chinese medicinal and edible plant. The structures of these natural compounds were elucidated based on NMR, HRESIMS, single-crystal X-ray diffraction, and ECD spectroscopic data. Among the tested isolates (50 µg/mL), the inhibitory effects of irpexolaceus A, C, D, F, and G, irpexonjust B, and irpexlacte B against NO release from LPS-induced RAW 264.7 cells were higher than 45%, while irpexlacte C (42.6%), irpexolaceus B (39.6%), irpexonjust A (43.7%), and irpexolaceus E (33.6%) exhibited weaker inhibitory effects on the release of NO.

6.
Int J Surg Case Rep ; 89: 106590, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34784532

RESUMO

INTRODUCTION AND IMPORTANCE: To describe an unusual case with a primary hepatic neuroendocrine tumour (PHNET) with multiple liver metastases. CASE PRESENTATION: We reported a 65-year-old woman with PHNET with multiple liver metastases. She was highly suspected of having primary liver cancer with multiple intrahepatic metastases before liver biopsy, but was diagnosed with PHNET with multiple liver metastases after histopathology and immunohistochemistry (IHC) examinations. The patient successfully underwent three times of transcatheter arterial chemoembolization (TACE), and is currently living in a good state without related complications. CLINICAL DISCUSSION: Neuroendocrine tumors (NETs), also known as carcinoids or argyrophilic tumors, are very rare malignant tumors. The liver is the main metastasis site of NETs, but primary hepatic neuroendocrine tumors (PHNETs) are extremely rare. Histopathology and immunohistochemistry (IHC) examinations are still the main methods used for diagnosing NETs. There are no treatment guidelines for PHNETs, and surgical resection is generally the preferred treatment. For PHNET patients who are not suitable for surgery, TACE has been proven to be an effective alternative treatment that can effectively reduce the tumour burden and relieve symptoms, but the current evidence is still limited. CONCLUSION: The clinical diagnosis of PHNET still faces great challenges, imaging examinations often lead to misdiagnosis, and its diagnosis mainly depends on histopathology and immunohistochemical examinations. For PHNET patients who are not suitable for surgery, TACE may be an effective alternative therapy.

7.
Int J Mol Sci ; 22(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34769365

RESUMO

Loach (Misgurnus anguillicaudatus) is well known to perform air-breathing through the posterior intestine and skin. However, we find here for the first time a unique central vascular structure in the loach barbel, with a blood-gas diffusion distance as short as that of the posterior intestine. Under acute hypoxia, the distance of loach barbels became significantly shorter. Moreover, barbel removal significantly decreased air-breathing frequency of the loach. These findings imply that the barbel is another air-breathing organ of the loach. For further investigation of loach barbel air-breathing, a transcriptome analysis of barbels with air exposure treatment was performed. A total of 2546 differentially expressed genes (DEGs) between the T-XU (air exposure) and C-XU (control) group were identified, and 13 key DEGs related to barbel air-breathing were screened out. On this foundation, sequence, expression, and location analysis results indicated an important positive role of fibronectin 1b (fn1b) in loach barbel air-breathing. We further generated an fn1b-depletion loach (MT for short) using the CRISPR/Cas9 technique. It was indicated that depletion of fn1b could weaker barbel air-breathing ability. In conclusion, due to nonlethal and regenerative characteristics, the loach barbel, a newly discovered and fn1b-related fish air-breathing organ, can be a good model for fish air-breathing research.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34839401

RESUMO

Air-breathing has evolved independently serval times with a variety of air-breathing organs (ABOs) in fish. The physiology of the air-breathing in bimodal respiration fish has been well understood, while studies on molecular mechanisms of the character are very limited. In the present study, we first determined the gill indexes of 110 fish species including 25 and 85 kinds of bimodal respiration fishes and non-air-breathing fishes, respectively. Then combined with histological observations of gills and ABOs/non-ABOs in three bimodal respiration fishes and two non-air breathing fishes, we found that the bimodal respiration fish was always of a degeneration gill and a well-vascularized ABO. Meanwhile, a comparative transcriptome analysis of posterior intestines, namely a well vascularized ABO in Misgurnus anguillicaudatus and a non-ABO in Leptobotia elongata, was performed to expound molecular variations of the air-breathing character. A total of 5,003 orthologous genes were identified. Among them, 1,189 orthologous genes were differentially expressed, which were enriched in 14 KEGG pathways. More specially, the expressions of hemoglobin genes and various HIF/VEGF signaling pathway genes were obviously upregulated in the ABO of M. anguillicaudatus. Moreover, we found that HIF-1α, VEGFAa, and MAP2K1 were co-expressed dramatically higher in ABOs of bimodal respiration fishes than those of non-ABOs of non-air-breathing fishes. These results indicated that the HIF/VEGF pathway played an important role in ABO angiogenesis/formation to promote fish to do aerial respiration. This study will contribute to our understanding of molecular mechanisms of air-breathing in fish.

9.
Nat Prod Res ; : 1-7, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34842007

RESUMO

Nine compounds were isolated and elucidated from this species, among which, two new compounds (1, 2) and seven known compounds (3-9). Their structures were determined by means of extensively spectroscopic analysis including HR-ESI-MS, 1H NMR, 13C NMR, HSQC and HMBC. The bioactivities evaluation was referred to the cytotoxic assay on four human tumor cell lines of the ethanol extract, different fractions and 6 compounds. The results demonstrated that the dichloromethane fraction showed the strongest cytotoxicity, followed by the ethyl acetate fraction. Compounds 4 and 6 had significant effects on SMMC-7721 and Hela cells.

10.
Sci China Life Sci ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34846643

RESUMO

The changes associated with malignancy are not only in cancer cells but also in environment in which cancer cells live. Metabolic reprogramming supports tumor cell high demand of biogenesis for their rapid proliferation, and helps tumor cell to survive under certain genetic or environmental stresses. Emerging evidence suggests that metabolic alteration is ultimately and tightly associated with genetic changes, in particular the dysregulation of key oncogenic and tumor suppressive signaling pathways. Cancer cells activate HIF signaling even in the presence of oxygen and in the absence of growth factor stimulation. This cancer metabolic phenotype, described firstly by German physiologist Otto Warburg, insures enhanced glycolytic metabolism for the biosynthesis of macromolecules. The conception of metabolite signaling, i.e., metabolites are regulators of cell signaling, provides novel insights into how reactive oxygen species (ROS) and other metabolites deregulation may regulate redox homeostasis, epigenetics, and proliferation of cancer cells. Moreover, the unveiling of noncanonical functions of metabolic enzymes, such as the moonlighting functions of phosphoglycerate kinase 1 (PGK1), reassures the importance of metabolism in cancer development. The metabolic, microRNAs, and ncRNAs alterations in cancer cells can be sorted and delivered either to intercellular matrix or to cancer adjacent cells to shape cancer microenvironment via media such as exosome. Among them, cancer microenvironmental cells are immune cells which exert profound effects on cancer cells. Understanding of all these processes is a prerequisite for the development of a more effective strategy to contain cancers.

11.
Lipids Health Dis ; 20(1): 127, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602076

RESUMO

BACKGROUND: Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway. METHODS: We downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting the endoglin gene in human umbilical vein endothelial cells (HUVECs) and validated by western blotting. The related genes and pathways regulated by endoglin were obtained by analysing the sequencing data. RESULTS: Research has shown that interference with endoglin can promote the proliferation and migration and significantly inhibit the apoptosis of vascular endothelial cells. Interference with endoglin particularly encourages the expression of VEGFB in vascular endothelial cells. CONCLUSION: The endoglin gene in vascular endothelial cells regulates the PI3K-Akt, Wnt, TNF, and cellular metabolism pathways by activating the SMAD pathway. RAB26, MR1, CCL2, SLC29A4, IBTK, VEGFB, and GOLGA8B play critical roles. Endoglin interacts closely with 11 proteins such as CCL2 and SEPRINE1, which participate in the vital pathway of plaque formation. Interference with endoglin can alter the course of coronary atherosclerosis.

12.
Curr Zool ; 67(4): 411-418, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34616938

RESUMO

Coordination and consensus in collective behavior have attracted a lot of research interest. Although previous studies have investigated the role of compromisers in group consensus, they provide little insight into why compromisers would allow such social arrangements to persist. In this study, the potential relationship between group movements and conflict management in Tibetan macaques in Anhui province, China, was investigated using hierarchical cluster analyses. Some members with higher social centrality or social rank often formed a front-runner cluster during group movements. They had higher leadership success than individuals outside the front-runner cluster. Other members with lower social centrality or social rank often followed the group movements initiated by the front-runner cluster, and thus formed the compromiser cluster. Compromisers' proximity relations with front-runners increased with their following scores to front-runners. Compromisers had fewer events of being attacked when they followed group movements initiated by the front-runners. The compromising process made compromisers lose the choice of direction preference, but it could increase their individual safeties. This trade-off suggests that compromisers play a role of decision-maker in coordination and consensus scenarios among social animals.

13.
Front Microbiol ; 12: 737626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630364

RESUMO

Quorum sensing (QS) and biofilm formation inhibition activity of esculetin on Aeromonas hydrophila SHAe 115 were evaluated. Exposure to esculetin at 25, 50, and 100µg/ml significantly inhibited the production of protease and hemolysin, the formation of biofilms and attenuated the swarming motility of A. hydrophila SHAe 115. Biofilm forming inhibition was also observed through confocal laser scanning microscopy and scanning electron microscope. Quantitative real-time PCR analysis indicated that genes positively related to QS and biofilm formation were downregulated to varying degrees, while gene (litR) negatively related to biofilm formation was significantly upregulated. The phenotypic results were in good agreement with gene expression levels. These results indicated that esculetin would be a potential QS inhibitor for A. hydrophila.

14.
J Am Chem Soc ; 143(42): 17701-17707, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34618453

RESUMO

Covalent organic frameworks (COFs) with efficient charge transport and exceptional chemical stability are emerging as an import class of semiconducting materials for opto-/electronic devices and energy-related applications. However, the limited synthetic chemistry to access such materials and the lack of mechanistic understanding of carrier mobility greatly hinder their practical applications. Herein, we report the synthesis of three chemically stable polyarylether-based metallophthalocyanine COFs (PAE-PcM, M = Cu, Ni, and Co) and facile in situ growth of their thin films on various substrates (i.e., SiO2/Si, ITO, quartz) under solvothermal conditions. We show that PAE-PcM COFs thin films with van der Waals layered structures exhibit p-type semiconducting properties with the intrinsic mobility up to ∼19.4 cm2 V-1 s-1 and 4 orders of magnitude of increase in conductivity for PAE-PcCu film (0.2 S m-1) after iodine doping. Density functional theory calculations reveal that the carrier transport in the framework is anisotropic, with the out-of-plane hole transport along columnar stacked phthalocyanine more favorable. Furthermore, PAE-PcCo shows the redox behavior maximumly contributes ∼88.5% of its capacitance performance, giving rise to a high surface area normalized capacitance of ∼19 µF cm-2. Overall, this work not only offers fundamental understandings of electronic properties of polyarylether-based 2D COFs but also paves the way for their energy-related applications.

15.
Nanomaterials (Basel) ; 11(10)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34685159

RESUMO

The spin related electrical and thermoelectric properties of monolayer and bilayer MPc (M = Co, Fe, Cu) molecular devices in a parallel spin configuration (PC) and an anti-parallel spin configuration (APC) between the V-shaped zigzag-edged graphene nanoribbon electrodes and the center bilayer MPc molecules are investigated by combining the density functional theory and non-equilibrium Green's function approaches. The results show that there is an ultrahigh spin filter efficiency exceeding 99.99995% and an ultra-large total conductance of 0.49996G0 for FePc-CoPc molecular devices in the PC and a nearly pure charge current at high temperature in the APC and a giant MR ratio exceeding 9.87 × 106% at a zero bias. In addition, there are pure spin currents for CuPc and FePc molecular devices in the PC, and an almost pure spin current for FePc molecular devices in the APC at some temperature. Meanwhile, there is a high SFE of about 99.99585% in the PC and a reserved SFE of about -19.533% in the APC and a maximum MR ratio of about 3.69 × 108% for the FePc molecular device. Our results predict that the monolayer and bilayer MPc (M = Co, Fe, Cu) molecular devices possess large advantages in designing high-performance electrical and spintronic molecular devices.

16.
Dalton Trans ; 50(43): 15849-15854, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34708848

RESUMO

Uniform lithium deposition is a benefit to achieving high-energy-density lithium metal batteries. There are many effective methods to suppress the dendritic growth of metallic lithium and promote the application of the lithium anode. However, the designation of lithiophilic sites at the atomic level remains a huge challenge. Herein, a two-dimensional porous conjugated porphyrin polymer linked by two acetylenic linkages from an in situ coupling reaction has been prepared on copper foil and employed as the lithiophilic host. The four electron-rich pyrrolic nitrogen atoms in the porphyrin building block and the linkage electron-rich sp-hybridized carbon atoms were regarded as precise lithiophilic sites, resulting in a decreased nucleation overpotential and dendrite free morphology. With uniform lithium deposition, the electrochemical performance of the electrode was significantly improved in regard to the overpotential, coulombic efficiency and lifespan. This work expands the precise construction of lithiophilic sites at the atomic level and benefits to further development of high-energy density lithium metal batteries.

17.
Genome Med ; 13(1): 164, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649620

RESUMO

BACKGROUND: The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. METHODS: Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. RESULTS: Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. CONCLUSIONS: Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19 , Evasão da Resposta Imune , Mutação , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Adulto , Idoso , Linfócitos B/imunologia , COVID-19/genética , COVID-19/imunologia , Feminino , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
18.
J Nanobiotechnology ; 19(1): 351, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717639

RESUMO

BACKGROUND: Multi-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community. However, low accumulation at the tumor sites and quick immune clearance of the anti-tumor agents are still insurmountable challenges. Hypothetically, cancer cell membrane (CCM) can homologously target the tumor whereas multi-modal therapy can complement the disadvantages of singular therapies. Meanwhile, moderate hyperthermia induced by photothermal therapy can boost the cellular uptake of therapeutic agents by cancer cells. RESULTS: CCM-cloaked indocyanine green (ICG)-incorporated and abraxane (PTX-BSA)-loaded layered double hydroxide (LDH) nanosheets (LIPC NSs) were fabricated for target efficient photo-chemotherapy of colorectal carcinoma (CRC). The CCM-cloaked LDH delivery system showed efficient homologous targeting and cytotoxicity, which was further enhanced under laser irradiation to synergize CRC apoptosis. On the other hand, CCM-cloaking remarkably reduced the uptake of LDH NSs by HEK 293T cells and macrophages, implying mitigation of the side effects and the immune clearance, respectively. In vivo data further exhibited that LIPC NSs enhanced the drug accumulation in tumor tissues and significantly retarded tumor progression under laser irradiation at very low therapeutic doses (1.2 and 0.6 mg/kg of ICG and PTX-BSA), without observed side effects on other organs. CONCLUSIONS: This research has demonstrated that targeting delivery efficiency and immune-escaping ability of LIPC NSs are tremendously enhanced by CCM cloaking for efficient tumor accumulation and in situ generated hyperthermia boosts the uptake of LIPC NSs by cancer cells, a potential effective way to improve the multi-modal cancer therapy.

19.
Stem Cell Res Ther ; 12(1): 523, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620239

RESUMO

BACKGROUND: Integrins play a prominent role in osteogenic differentiation by transmitting both mechanical and chemical signals. Integrin expression is closely associated with tensile stress, which has a positive effect on osteogenic differentiation. We investigated the relationship between integrin αVß3 and tensile stress. METHODS: Human fibroblasts were treated with c (RGDyk) and lentivirus transduction to inhibit function of integrin αVß3. Y-15, cytochalasin D and verteporfin were used to inhibit phosphorylation of FAK, polymerization of microfilament and function of nuclear YAP, respectively. Fibroblasts were exposed to a cyclic tensile stress of 10% at 0.5 Hz, once a day for 2 h each application. Fibroblasts were harvested on day 4 and 7 post-treatment. The expression of ALP, RUNX2, integrin αVß3, ß-actin, talin-1, FAK, vinculin, and nuclear YAP was detected by Western blot or qRT-PCR. The expression and distribution of integrin αVß3, vinculin, microfilament and nuclear YAP. RESULTS: Cyclic tensile stress was found to promote expression of ALP and RUNX2. Inhibition of integrin αVß3 activation downregulated the rearrangement of microfilament and the expression of ALP, RUNX2 and nuclear YAP. When the polymerization of microfilament was inhibited the expression of ALP, RUNX2 and nuclear YAP were decreased. The phosphorylation of FAK induced by cyclic tensile stress reduced by the inhibition of integrin αVß3. The expression of ALP and RUNX2 was decreased by inhibition of phosphorylation of FAK and inhibition of nuclear YAP. CONCLUSIONS: Cyclic tensile stress promotes osteogenesis of human fibroblasts via integrin αVß3-microfilament axis. Phosphorylation of FAK and nuclear YAP participates in this process.


Assuntos
Fibroblastos/citologia , Integrina alfaVbeta3 , Osteogênese , Citoesqueleto de Actina , Células Cultivadas , Humanos , Estresse Mecânico
20.
Cell Death Discov ; 7(1): 263, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561426

RESUMO

Apoptosis is a strictly coordinated process to eliminate superfluous or damaged cells, and its deregulation leads to birth defects and various human diseases. The regulatory mechanism underlying apoptosis still remains incompletely understood. To identify novel components in apoptosis, we carry out a modifier screen and find that the Hh pathway aggravates Hid-induced apoptosis. In addition, we reveal that the Hh pathway triggers apoptosis through its transcriptional target gene rdx, which encodes an E3 ubiquitin ligase. Rdx physically binds Diap1 to promote its K63-linked polyubiquitination, culminating in attenuating Diap1-Dronc interaction without affecting Diap1 stability. Taken together, our findings unexpectedly uncover the oncogenic Hh pathway is able to promote apoptosis through Ci-Rdx-Diap1 module, raising a concern to choose Hh pathway inhibitors as anti-tumor drugs.

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