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2.
J Nat Prod ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596414

RESUMO

Nine new highly oxygenated 3,5-dimethylorsellinic acid-derived meroterpenoids, talaromynoids A-I (1-9), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated by HRMS, NMR, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculations. Compounds 1 and 7-9 possessed unprecedented 5/7/6/5/6/6, 6/7/6/6/6/5, 6/7/6/5/6/5/4, and 7/6/5/6/5/4 polycyclic systems, respectively. Biologically, compound 5 showed selective inhibitory activity against phosphatase CDC25B with an IC50 value of 13 µM. Moreover, 7-9 and 12 exhibited the activity of reducing triglyceride in 3T3-L1 adipocytes in a dosage-dependent manner.

3.
Mol Cancer Res ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654722

RESUMO

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common EBV-associated head and neck malignancy. However, the effect of EBV on NPC LN metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF-1a hyperactivity and subsequent VEGF-C transcriptional activation. Additionally, administration of anti-VEGF-C antibody or HIF-1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF-1a and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis.

5.
Int J Pharm ; 609: 121162, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34624444

RESUMO

Antibodies targeting the CD40-CD40L pathway have great potential for treating autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), and inflammatory bowel diseases (IBD). However, in addition to the known difficulty in generating a purely antagonistic CD40 antibody, the presence of CD40 and CD40L on platelets creates additional unique challenges for the safety, target coverage, and clearance of antibodies targeting this pathway. Previously described therapeutic antibodies targeting this pathway have various shortcomings, and the full therapeutic potential of this axis has yet to be realized. Herein, we describe the generation and characterization of BI 655064, a novel, purely antagonistic anti-CD40 antibody that potently neutralizes CD40-CD40L-dependent B-cell stimulation without evidence of impacting platelet functions. This uniquely optimized antibody targeting a highly challenging pathway was obtained by applying stringent functional and biophysical criteria during the lead selection process. BI 655064 has favorable target-mediated drug disposition (TMDD)-saturation pharmacokinetics, consistent with that of a high-quality therapeutic monoclonal antibody.

6.
BMC Med Imaging ; 21(1): 133, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530768

RESUMO

BACKGROUND: To compare the changes in quantitative parameters and the size and degree of 18F-fluorodeoxyglucose ([18F]FDG) uptake of malignant tumor lesions between Bayesian penalized-likelihood (BPL) and non-BPL reconstruction algorithms. METHODS: Positron emission tomography/computed tomography images of 86 malignant tumor lesions were reconstructed using the algorithms of ordered subset expectation maximization (OSEM), OSEM + time of flight (TOF), OSEM + TOF + point spread function (PSF), and BPL. [18F]FDG parameters of maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and signal-to-background ratio (SBR) of these lesions were measured. Quantitative parameters between the different reconstruction algorithms were compared, and correlations between parameter variation and lesion size or the degree of [18F]FDG uptake were analyzed. RESULTS: After BPL reconstruction, SUVmax, SUVmean, and SBR were significantly increased, MTV was significantly decreased. The difference values of %ΔSUVmax, %ΔSUVmean, %ΔSBR, and the absolute value of %ΔMTV between BPL and OSEM + TOF were 40.00%, 38.50%, 33.60%, and 33.20%, respectively, which were significantly higher than those between BPL and OSEM + TOF + PSF. Similar results were observed in the comparison of OSEM and OSEM + TOF + PSF with BPL. The %ΔSUVmax, %ΔSUVmean, and %ΔSBR were all significantly negatively correlated with the size and degree of [18F]FDG uptake in the lesions, whereas significant positive correlations were observed for %ΔMTV and %ΔTLG. CONCLUSION: The BPL reconstruction algorithm significantly increased SUVmax, SUVmean, and SBR and decreased MTV of tumor lesions, especially in small or relatively hypometabolic lesions.

7.
J Org Chem ; 86(18): 12831-12839, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34477382

RESUMO

(+)- and (-)-talaromyoxaones A and B (1 and 2, respectively), two new oxaphenalenone derivatives with a hemiacetal frame and an unprecedented spirolactone frame of a 2'H,3H,4'H-spiro[isobenzofuran-1,3'-pyran]-3-one unit that show biosynthetic enantiodivergence, and two new oxaphenalenone analogues (±)-11-apopyrenulin (3) and (+)- or (-)-abeopyrenulin (4) were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations of ECD spectra. Compounds 1 and 2 showed selective inhibitory activity against phosphatases SHP1, SHP2, and MEG2 with IC50 values of 1.3-3.4 µM, and the potential modes of action for 1 were investigated by a preliminary molecular docking study.


Assuntos
Talaromyces , Simulação de Acoplamento Molecular , Monoéster Fosfórico Hidrolases , Espironolactona
8.
Circulation ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34503349

RESUMO

Background: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain (AL) amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac AL amyloidosis. Methods: This was a multicenter, open-label randomized controlled trial. Patients with Mayo 2004 stage II-III AL amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression or organ progression (heart, kidney or liver). Hematologic progression was defined based on substantial increase in free light chain. Increase in either N-terminal pro B-type natriuretic peptide or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated using a Cox regression model. Results: 140 patients underwent randomization, with 70 in each group. The median age was 61 (range, 33-78) years with a male: female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32/70 (45.7%) of patients in the doxycycline group and 30/70 (42.9%) of patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio 0.97, 95% CI, 0.59-1.60, p=0.91). Cardiac progression occurred in 29/70 (41.4%) of patients in the doxycycline group and 26/70 (37.1%) of patients in the control group. The death rates for both groups by the end of follow-up was the same, 25/70 (35.7%). There were no significant differences observed for either cardiac PFS (hazard ratio 0.91, 95% CI, 0.54-1.55, p=0.74) or overall survival (hazard ratio 1.04, 95% CI, 0.60-1.81, p=0.89). Conclusions: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac AL amyloidosis. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03401372.

9.
Cell Mol Immunol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556823

RESUMO

Immunomodulation is considered a potential therapeutic approach for chronic kidney disease (CKD). Although it has been previously reported that CD4+ T cells contribute to the development of renal fibrosis, the role of MHC class II (MHCII) in the development of renal fibrosis remains largely unknown. The present study reports that the expression of MHCII molecules in renal cortical tubules is upregulated in mouse renal fibrosis models generated by unilateral ureter obstruction (UUO) and folic acid (FA). Proximal tubule epithelial cells (PTECs) are functional antigen-presenting cells that promote the proliferation of CD4+ T cells in an MHCII-dependent manner. PTECs from mice with renal fibrosis had a stronger ability to induce T cell proliferation and cytokine production than control cells. Global or renal tubule-specific ablation of H2-Ab1 significantly alleviated renal fibrosis following UUO or FA treatment. Renal expression of profibrotic genes showed a consistent reduction in H2-Ab1 gene-deficient mouse lines. Moreover, there was a marked increase in renal tissue CD4+ T cells after UUO or FA treatment and a significant decrease following renal tubule-specific ablation of H2-Ab1. Furthermore, renal tubule-specific H2-Ab1 gene knockout mice exhibited higher proportions of regulatory T cells (Tregs) and lower proportions of Th2 cells in the UUO- or FA-treated kidneys. Finally, Immunohistochemistry (IHC) studies showed increased renal expression of MHCII and the profibrotic gene α smooth muscle actin (α-SMA) in CKD patients. Together, our human and mouse data demonstrate that renal tubular MHCII plays an important role in the pathogenesis of renal fibrosis.

10.
Int J Hyperthermia ; 38(1): 1304-1312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468276

RESUMO

BACKGROUND: Several studies have reported the combination of intracavity or cervical lymph node hyperthermia with chemoradiotherapy (CRT) to improve clinical outcomes in nasopharyngeal carcinoma (NPC), but the combination with whole-body hyperthermia (WBH) for treating NPC is unexplored. We aimed to assess the efficacy of the combination of radiotherapy, chemotherapy and WBH in patients with locoregionally advanced NPC. METHODS: Between July 2008 and November 2012, 239 newly diagnosed NPC patients were enrolled in a pre-propensity score-matched cohort, including 193 patients who received CRT (CRT group) and 46 who underwent CRT with WBH (HCRT group). The feasibility and clinical outcomes of both groups were evaluated and toxicities assessed. Survival rates were assessed using the Kaplan-Meier method, log-rank test and Cox regression. RESULTS: Following propensity score matching, 46 patients from each group were included. The 5-year overall survival (OS) rates were 65.2% in the CRT group and 80.3% in the HCRT group (p=.027). In contrast, the other survival outcomes at 5 years were similar between the groups: locoregional recurrence-free survival (LRRFS), 74.7% vs. 87.6% (p=.152); distant metastasis-free survival (DMFS), 67.4% vs. 77.9% (p=.125); and progression-free survival (PFS), 53.1% vs. 69.2% (p=.115). In the multivariate analyses, the only two independent predictors of OS were clinical stage and HCRT. CONCLUSIONS: These results suggest that WBH, when combined with CRT, can improve the OS of patients with advanced NPC.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Quimiorradioterapia , Humanos , Hipertermia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Pontuação de Propensão , Estudos Retrospectivos
11.
Sensors (Basel) ; 21(18)2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34577327

RESUMO

Toxic and nontoxic volatile organic compound (VOC) gases are emitted into the atmosphere from certain solids and liquids as a consequence of wastage and some common daily activities. Inhalation of toxic VOCs has an adverse effect on human health, so it is necessary to monitor their concentration in the atmosphere. In this work, we report on the fabrication of inorganic nanotube (INT)-tungsten disulfide, paper-based graphene-PEDOT:PSS sheet and WS2 nanotube-modified conductive paper-based chemiresistors for VOC gas sensing. The WS2 nanotubes were fabricated by a two-step reaction, that is oxide reduction and sulfurization, carried out at 900 °C. The synthesized nanotubes were characterized by FE-SEM, EDS, XRD, Raman spectroscopy, and TEM. The synthesized nanotubes were 206-267 nm in diameter. The FE-SEM results show the length of the nanotubes to be 4.5-8 µm. The graphene-PEDOT:PSS hybrid conductive paper sheet was fabricated by a continuous coating process. Then, WS2 nanotubes were drop-cast onto conductive paper for fabrication of the chemiresistors. The feasibility and sensitivity of the WS2 nanotube-modified paper-based chemiresistor were tested in four VOC gases at different concentrations at room temperature (RT). Experimental results show the proposed sensor to be more sensitive to butanol gas when the concentration ranges from 50 to 1000 ppm. The limit of detection (LOD) of this chemiresistor for butanol gas was 44.92 ppm. The WS2 nanotube-modified paper-based chemiresistor exhibits good potential as a VOC sensor with the advantages of flexibility, easy fabrication, and low fabrication cost.


Assuntos
Nanotubos , Compostos Orgânicos Voláteis , Dissulfetos , Humanos , Limite de Detecção , Tungstênio
12.
Zookeys ; 1059: 35-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566446

RESUMO

Nidiranaguangxiensis sp. nov., a new music frog species, is proposed, based on a series of specimens collected from Mt Daming, Guangxi, southern China. The new species is close to N.yeae, N.daunchina, N.yaoica, and N.chapaensis from southwestern and south-central China and northern Indochina, while the relationships among these species remain unresolved. Nidiranaguangxiensis sp. nov. can be distinguished from all known congeners by the genetic divergences in the mitochondrial 16S and COI genes, the behavior of nest construction, the advertisement call containing 6-11 rapidly repeated regular notes, and a combination of morphological characteristics. Furthermore, the Nidirana populations recorded in Guangxi are clarified in this work, providing valuable new information on the knowledge of the genus Nidirana.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 889-895, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34535202

RESUMO

OBJECTIVES: To investigate the incidence of maternal group B Streptococcus (GBS) colonization and neonatal early-onset GBS disease (GBS-EOD), and to study the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. METHODS: A total of 16 384 pregnant women and 16 634 neonates delivered by them were enrolled prospectively who had medical records in Xiamen Maternal and Child Care Hospital, Beijing Obstetrics and Gynecology Hospital of Capital Medical University, and Zhangzhou Zhengxing Hospital from May 1, 2019 to April 30, 2020. Unified GBS screening time, culture method, and indication for intrapartum antibiotic prophylaxis (IAP) were adopted in the three hospitals. The incidence rates of maternal GBS colonization and neonatal GBS-EOD were investigated. A multivariate logistic regression analysis was used to identify the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. RESULTS: In these three hospitals, the positive rate of GBS culture among the pregnant women in late pregnancy was 11.29% (1 850/16 384), and the incidence rate of neonatal GBS-EOD was 0.96‰ (16/16 634). The admission rate of live infants born to the GBS-positive pregnant women was higher than that of those born to the GBS-negative ones (P<0.05). The live infants born to the GBS-positive pregnant women had a higher incidence rate of GBS-EOD than those born to the GBS-negative ones [6.38‰ (12/1 881) vs 0.27‰ (4/14 725), P<0.05]. The multivariate logistic regression analysis showed that placental swabs positive for GBS and positive GBS in neonatal gastric juice at birth were independent predictive factors for the development of GBS-EOD (P<0.05), while adequate IAP was a protective factor (P<0.05) in the offspring of pregnant women with GBS colonization. CONCLUSIONS: GBS colonization of pregnant women in late pregnancy has adverse effects on their offspring. It is important to determine prenatal GBS colonization status of pregnant women and administer with adequate IAP based on the indications of IAP to reduce the incidence of neonatal GBS-EOD. Citation.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Antibioticoprofilaxia , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Placenta , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Prospectivos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae
14.
J Environ Manage ; 299: 113607, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467864

RESUMO

Traditional Chinese medicine (TCM) has wide application and important functions in curing many diseases, but a great number of herb residues are usually generated after its manufacture and usage. Without proper and timely treatment, these traditional Chinese medicinal herb (TCMH) residues will cause some environmental pollution. In addition to treatment, bioresources utilization of TCMH residues is also important for its great potential as a suitable feedstock for the production of energy, materials, and chemicals. In this situation, advanced and well-designed solid waste management is important to make the TCM industry environmentally friendly and economically attractive. In this review article, the recent progress focusing on various methods for TCMH residues treatment and bioresources utilization are introduced in detail. In particular, the technologies for thermochemical conversion and biochemical conversion of TCMH residues are mainly focused on in order to show how to fulfill effective and efficient bioresources utilization. Besides, some other technologies which are suitable for the treatment and bioresources utilization of TCMH residues are presented as well. Finally, some industrial prospects are given from the economic, operational, and environmental aspects for the further development of treatment and bioresources utilization of TCMH residues. Overall, this work can provide some systematical and comprehensive information for the development of technologies that help sustainably manage the herb residues generated in the TCM industry.


Assuntos
Plantas Medicinais , China , Medicina Tradicional Chinesa
15.
Cell Discov ; 7(1): 71, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408130

RESUMO

Massive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris (P. pastoris) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.

16.
Inflamm Res ; 70(9): 959-969, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34390377

RESUMO

BACKGROUND: Donor cell-derived exosomes regulate recipient cell functions. The aim of this study was to investigate the effect of human normal bladder stromal cell (hBSC) derived exosomal miR-217 on bladder cell cancer proliferation and migration. METHODS: Human BSCs were transfected with miR-217 mimic or inhibitor and hBSC-derived exosomes were isolated. Human bladder cancer cell lines (T24 and 5367) were co-cultured with hBSC-derived exosomal miR-217 mimic or inhibitor. Proliferation, migration, and apoptosis of the bladder cancer cells were assessed by Edu assay, Transwell migration assay, and Annexin V assay. RESULTS: Expression of miR-217 was significantly higher in the T24 and 5367 cell lines (P < 0.01). Exosomal miR-217 mimic enhanced proliferation and migration of T24 and 5367 cells, but inhibited apoptosis of the cells (P < 0.01); in contrast, exosomal miR-217 inhibitor suppressed proliferation and migration but stimulated apoptosis of the two cancer cell lines (P < 0.01). Moreover, exosomal miR-217 mimic stimulated YAP and its target proteins including Cyr61, CTGF, and ANKRD1 (P < 0.01), and in contrast, exosomal miR-217 inhibitor suppressed YAP and its target proteins (P < 0.01). CONCLUSION: These findings suggested that hBSC-derived exosomal miR-217 may act as oncogene in bladder cancer cells, and that Hippo-YAP signaling pathway maybe the target for miR-217 in the bladder cancer cell lines.

17.
ACS Appl Mater Interfaces ; 13(33): 39394-39403, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34392674

RESUMO

A kind of silicone rubber (SR)/paraffin (Pa)@silicon dioxide (SiO2)@polydopamine (PDA) phase-change composite was prepared in this work. The double-shelled Pa@SiO2@PDA phase-change microcapsules were constructed by oxidative self-polymerization of dopamine (DA) in Tris-HCl buffer solution. The effect of the DA content on the properties of Pa@SiO2@PDA microcapsules and SR/Pa@SiO2@PDA composites was researched. Due to the protective effect of SiO2, PDA layer, and SR matrix, the SR/Pa@SiO2@PDA composites have good leak-proofing performance, and the leakage rate of SR/Pa@SiO2@PDA-2 is as low as 0.45%. Phase-change enthalpies of the Pa@SiO2@PDA microcapsules and SR/Pa@SiO2@PDA composites are reduced slightly with increasing DA content. Meanwhile, the composites displayed improved mechanical strength. The tensile strength of SR/Pa@SiO2@PDA-2 can be up to 0.560 MPa, which is 1.85 times higher than the tensile strength of pure SR/Pa@SiO2 because the interface compatibility between Pa@SiO2 microcapsules and SR is improved through hydrogen bonding between the abundant groups on the PDA surface and the matrix. Moreover, the rough surface of the PDA-modified microcapsules also enhances the interface interaction through physical "interlocking". The new kind of SR/Pa@SiO2@PDA composite can be used for thermal management.

18.
Nanomaterials (Basel) ; 11(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34443870

RESUMO

We study theoretically the Fano resonances (FRs) produced by the near-field coupling between the lowest-order (dipolar) sphere plasmon resonance and the dipolar cavity plasmon mode supported by an Ag nanoshell or the hybrid mode in a simple three-layered Ag nanomatryushka constructed by incorporating a solid Ag nanosphere into the center of Ag nanoshell. We find that the linewidth of dipolar cavity plasmon resonance or hybrid mode induced FR is as narrow as 6.8 nm (corresponding to a high Q-factor of ~160 and a long dephasing time of ~200 fs) due to the highly localized feature of the electric-fields. In addition, we attribute the formation mechanisms of typical asymmetrical Fano line profiles in the extinction spectra to the constructive (Fano peak) and the destructive interferences (Fano dip) arising from the symmetric and asymmetric charge distributions between the dipolar sphere and cavity plasmon or hybrid modes. Interestingly, by simply adjusting the structural parameters, the dielectric refractive index required for the strongest FR in the Ag nanomatryushka can be reduced to be as small as 1.4, which largely reduces the restriction on materials, and the positions of FR can also be easily tuned across a broad spectral range. The ultranarrow linewidth, highly tunability together with the huge enhancement of electric fields at the FR may find important applications in sensing, slow light, and plasmon rulers.

19.
Breast Cancer ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34351577

RESUMO

BACKGROUND: Breast cancer (BC) is one of the most common malignant tumors in women. Accumulating studies have been reported that long non-coding RNA (lncRNA) SNHG5 is highly expressed in BC. However, the specific molecular mechanism of SNHG5 in BC is unclear. METHODS: Gene and protein expressions in BC cell were detected by qRT-PCR and western blotting. The proliferation and cell cycle were measured using colony formation assay and flow cytometry analysis, separately. The glucose consumption and lactate production were determined by using the glucose assay kit and lactate assay kit. A dual-luciferase reporter assay was performed to measure the interaction between miR-299 and SNHG5 or BACH1. RESULTS: SNHG5 and BACH1 expressions were increased in BC cell while miR-299 level was decreased. SNHG5 increased BACH1 expression by directly targeting miR-299. SNHG5 silencing or miR-299 overexpression suppressed the proliferation of BC cell, arrested the cell cycle in the G1 cell phase, and decreased the glucose consumption and lactate production of BC cell. However, inhibition of miR-299 or overexpression of BACH1 could reverse the inhibitory effects of sh-SNHG5 on cell proliferation and glycolysis in BC. CONCLUSION: SNHG5 promoted the BC cell growth and glycolysis through up-regulating BACH1 expression via targeting miR-299. These findings may improve the diagnostic and therapeutic approaches to BC.

20.
Viruses ; 13(8)2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34452287

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.


Assuntos
Anticorpos Amplamente Neutralizantes/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/genética , Humanos , Camundongos , Testes de Neutralização , SARS-CoV-2/classificação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
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