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1.
Med Res Rev ; 41(6): 2891-2892, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34632605
2.
Nanomaterials (Basel) ; 11(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684916

RESUMO

Rare Earth Upconversion nanoparticles (UCNPs) are a type of material that emits high-energy photons by absorbing two or more low-energy photons caused by the anti-stokes process. It can emit ultraviolet (UV) visible light or near-infrared (NIR) luminescence upon NIR light excitation. Due to its excellent physical and chemical properties, including exceptional optical stability, narrow emission band, enormous Anti-Stokes spectral shift, high light penetration in biological tissues, long luminescent lifetime, and a high signal-to-noise ratio, it shows a prodigious application potential for bio-imaging and photodynamic therapy. This paper will briefly introduce the physical mechanism of upconversion luminescence (UCL) and focus on their research progress and achievements in bio-imaging, bio-detection, and photodynamic therapy.

3.
Nat Commun ; 12(1): 5744, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593814

RESUMO

Next-generation terahertz (THz) sources demand lightweight, low-cost, defect-tolerant, and robust components with synergistic, tunable capabilities. However, a paucity of materials systems simultaneously possessing these desirable attributes and functionalities has made device realization difficult. Here we report the observation of asymmetric spintronic-THz radiation in Two-Dimensional Hybrid Metal Halides (2D-HMH) interfaced with a ferromagnetic metal, produced by ultrafast spin current under femtosecond laser excitation. The generated THz radiation exhibits an asymmetric intensity toward forward and backward emission direction whose directionality can be mutually controlled by the direction of applied magnetic field and linear polarization of the laser pulse. Our work demonstrates the capability for the coherent control of THz emission from 2D-HMHs, enabling their promising applications on the ultrafast timescale as solution-processed material candidates for future THz emitters.

4.
Pathol Int ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597441

RESUMO

The genetic alterations in the recurrent breast fibroepithelial tumors are poorly understood. In the present study, we aimed to investigate mediator protein complex subunit 12 (MED12) exon 2 and telomerase reverse transcriptase (TERT) promoter mutations in a series of primary and recurrent fibroepithelial tumors. Sanger sequencing for MED12 exon 2 and TERT promoter was performed in 26 pairs of primary and recurrent fibroepithelial tumors (19 pairs of phyllodes tumors and seven pairs of fibroadenomas). The relationship between the genotypes and clinicopathological variables was also analyzed. MED12 mutation was identified in 19 primary tumors (12 phyllodes tumors and 7 fibroadenomas) and 17 recurrences (14 phyllodes tumors and three fibroadenomas). Most recurrent phyllodes tumors retained the original MED12 variants (17/19). Six recurrent fibroadenomas showed different MED12 variants from their paired primary tumors (6/7). TERT promoter mutation was identified in 13 primary phyllodes tumors (13/19) and 15 recurrent phyllodes tumors (15/19). However, it was only identified in one primary fibroadenoma (1/7). Recurrent phyllodes tumors often retained the original MED12 and TERT promoter mutations, while recurrent fibroadenomas often acquired new MED12 mutations. Our findings suggest that recurrent phyllodes tumors may be "true recurrence," and TERT mutant "benign fibroepithelial tumors" should be treated as phyllodes tumors.

5.
Nanoscale ; 13(31): 13231-13240, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477731

RESUMO

Although artemisinin (ART) has shown initial promise in cancer therapy, its therapeutic efficacy is limited by its low tumor inhibitory efficacy and unfavorable distribution. Considering the important role of heme in the specific parasite-killing effect of ART, we designed a liposomal nanostructure self-assembled from hemin-lipid (Hemesome) to co-deliver ART and hemin for cancer therapy. The synergistic chemotherapeutic and immunotherapeutic effects of hemin and ART were demonstrated both in vitro and in vivo. The liposome-like structure was relatively stable in the blood circulation and gastrointestinal tract environment, but dissociated in the tumor cell environment. The folic acid (FA) modification not only increased their efficiency for transport across the epithelium, but also increased their tumor accumulation. In mouse models, following oral administration of FA-Hemesome-ART nanoparticles (5 mg kg-1 ART in total) every other day and intraperitoneal injection with a programmed death-ligand 1 antibody (aPD-L1, 70 µg per mouse in total), MC38 tumors were completely inhibited within 30 days. The cured mice remained tumor-free 30 days after rechallenging them with another inoculation of MC38 cells due to the strong immune memory effect.


Assuntos
Artemisininas , Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Hemina , Imunoterapia , Lipídeos , Camundongos , Neoplasias/tratamento farmacológico
6.
Acta Pharm Sin B ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34567957

RESUMO

COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the globe, posing an enormous threat to public health and safety. Traditional Chinese medicine (TCM), in combination with Western medicine (WM), has made important and lasting contributions in the battle against COVID-19. In this review, updated clinical effects and potential mechanisms of TCM, presented in newly recognized three distinct phases of the disease, are summarized and discussed. By integrating the available clinical and preclinical evidence, the efficacies and underlying mechanisms of TCM on COVID-19, including the highly recommended three Chinese patent medicines and three Chinese medicine formulas, are described in a panorama. We hope that this comprehensive review not only provides a reference for health care professionals and the public to recognize the significant contributions of TCM for COVID-19, but also serves as an evidence-based in-depth summary and analysis to facilitate understanding the true scientific value of TCM.

8.
Adv Mater ; 33(39): e2103000, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34397123

RESUMO

The competing and non-equilibrium phase transitions, involving dynamic tunability of cooperative electronic and magnetic states in strongly correlated materials, show great promise in quantum sensing and information technology. To date, the stabilization of transient states is still in the preliminary stage, particularly with respect to molecular electronic solids. Here, a dynamic and cooperative phase in potassium-7,7,8,8-tetracyanoquinodimethane (K-TCNQ) with the control of pulsed electromagnetic excitation is demonstrated. Simultaneous dynamic and coherent lattice perturbation with 8 ns pulsed laser (532 nm, 15 MW cm-2 , 10 Hz) in such a molecular electronic crystal initiates a stable long-lived (over 400 days) conducting paramagnetic state (≈42 Ωcm), showing the charge-spin bistability over a broad temperature range from 2 to 360 K. Comprehensive noise spectroscopy, in situ high-pressure measurements, electron spin resonance (ESR), theoretical model, and scanning tunneling microscopy/spectroscopy (STM/STS) studies provide further evidence that such a transition is cooperative, requiring a dedicated charge-spin-lattice decoupling to activate and subsequently stabilize nonequilibrium phase. The cooperativity triggered by ultrahigh-strain-rate (above 106 s- 1 ) pulsed excitation offers a collective control toward the generation and stabilization of strongly correlated electronic and magnetic orders in molecular electronic solids and offers unique electro-magnetic phases with technological promises.

9.
J Neuroinflammation ; 18(1): 174, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372857

RESUMO

BACKGROUND: Celastrol (cel) was one of the earliest isolated and identified chemical constituents of Tripterygium wilfordii Hook. f. Based on a cel probe (cel-p) that maintained the bioactivity of the parent compound, the targets of cel in cerebral ischemia-reperfusion (I/R) injury were comprehensively analyzed by a quantitative chemical proteomics method. METHODS: We constructed an oxygen-glucose deprivation (OGD) model in primary rat cortical neurons and a middle cerebral artery occlusion (MCAO) model in adult rats to detect the direct binding targets of cel in cerebral I/R. By combining various experimental methods, including tandem mass tag (TMT) labeling, mass spectrometry, and cellular thermal shift assay (CETSA), we revealed the targets to which cel directly bound to exert neuroprotective effects. RESULTS: We found that cel inhibited the proinflammatory activity of high mobility group protein 1 (HMGB1) by directly binding to it and then blocking the binding of HMGB1 to its inflammatory receptors in the microenvironment of ischemia and hypoxia. In addition, cel rescued neurons from OGD injury in vitro and decreased cerebral infarction in vivo by targeting HSP70 and NF-κB p65. CONCLUSION: Cel exhibited neuroprotective and anti-inflammatory effects by targeting HSP70 and NF-κB p65 and directly binding to HMGB1 in cerebral I/R injury.

10.
Nat Commun ; 12(1): 4641, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330930

RESUMO

Surface states generally degrade semiconductor device performance by raising the charge injection barrier height, introducing localized trap states, inducing surface leakage current, and altering the electric potential. We show that the giant built-in electric field created by the surface states can be harnessed to enable passive wavelength conversion without utilizing any nonlinear optical phenomena. Photo-excited surface plasmons are coupled to the surface states to generate an electron gas, which is routed to a nanoantenna array through the giant electric field created by the surface states. The induced current on the nanoantennas, which contains mixing product of different optical frequency components, generates radiation at the beat frequencies of the incident photons. We utilize the functionalities of plasmon-coupled surface states to demonstrate passive wavelength conversion of nanojoule optical pulses at a 1550 nm center wavelength to terahertz regime with efficiencies that exceed nonlinear optical methods by 4-orders of magnitude.

11.
Nat Prod Rep ; 38(7): 1243-1250, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34287440

RESUMO

Covering: Up to 2020 Artemisinin has made a significant contribution towards global malaria control since its initial discovery. Countless lives have been saved by this unique and miraculous molecule. In 2006, artemisinin-based combination therapies (ACTs) were recommended by the World Health Organization (WHO) as the first-line treatment for uncomplicated malaria infection and have since remained as the mainstays of the antimalarial treatment. Even so, substantial efforts to pursue better curative effects for the treatment of malaria have never ceased, particularly with regards to the circumstances surrounding the appearance of delayed clearance of malaria parasites by 3 day ACT treatments in South-East Asian countries. Strategies to further optimize artemisinin-based therapies, including synthesizing better artemisinin derivatives, developing advanced drug delivery systems, and diversifying artemisinin partner drugs, have been proposed over the past few years. Here, we provide an updated account of the continuous efforts in improving ACTs for better efficacy in curing malarial infection.

12.
iScience ; 24(7): 102718, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34258553

RESUMO

Tumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30). We performed high-depth whole-exome sequencing of 206 tumor regions including 176 primary tumors, 19 LN, and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution and the evolution pattern of LCC and RC was more complex and divergent than RCC. Genetic and evolutionary evidences found that both LN and ENTD originated from different clones. Moreover, ENTD was a distinct entity from LN and evolved later.

13.
Signal Transduct Target Ther ; 6(1): 250, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34219129

RESUMO

Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer. Various endeavor has been made to explore the molecular biology basis of TNBC. Herein, we reported a novel function of factor Kinectin 1 (KTN1) as a carcinogenic promoter in TNBC. KTN1 expression in TNBC was increased compared with adjacent tissues or luminal or Her2 subtypes of breast cancer, and TNBC patients with high KTN1 expression have poor prognosis. In functional studies, knockdown of KTN1 inhibited the proliferation and invasiveness of TNBC both in vitro and in vivo, while overexpression of KTN1 promoted cancer cell proliferation and invasiveness. RNA-seq analysis revealed that the interaction of cytokine-cytokine receptor, particularly CXCL8 gene, was upregulated by KTN1, which was supported by the further experiments. CXCL8 depletion inhibited the tumorigenesis and progression of TNBC. Additionally, rescue experiments validated that KTN1-mediated cell growth acceleration in TNBC was dependent on CXCL8 both in vitro and in vivo. Furthermore, it was found that KTN1 enhanced the phosphorylation of NF-κB/p65 protein at Ser536 site, and specifically bound to NF-κB/p65 protein in the nucleus and cytoplasm of cells. Moreover, the transcription of CXCL8 gene was directly upregulated by the complex of KTN1 and NF-κB/p65 protein. Taken together, our results elucidated a novel mechanism of KTN1 gene in TNBC tumorigenesis and progression. KTN1 may be a potential molecular target for the development of TNBC treatment.

14.
Med Res Rev ; 41(6): 3156-3181, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34148245

RESUMO

Artemisinins are a family of sesquiterpene lactones originally derived from the sweet wormwood (Artemisia annua). Beyond their well-characterized role as frontline antimalarial drugs, artemisinins have also received increased attention for other potential pharmaceutical effects, which include antiviral, antiparsitic, antifungal, anti-inflammatory, and anticancer activities. With concerted efforts in further preclinical and clinical studies, artemisinin-based drugs have the potential to be viable treatments for a great variety of human diseases. Here, we provide a comprehensive update on recent reports of pharmacological actions and applications of artemisinins outside of their better-known antimalarial role and highlight their potential therapeutic viability for various diseases.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34131803

RESUMO

PURPOSE: To develop and evaluate the effectiveness of a deep learning framework (3D-ResNet) based on CT images to distinguish nontuberculous mycobacterium lung disease (NTM-LD) from Mycobacterium tuberculosis lung disease (MTB-LD). METHOD: Chest CT images of 301 with NTM-LD and 804 with MTB-LD confirmed by pathogenic microbiological examination were retrospectively collected. The differences between the clinical manifestations of the two diseases were analysed. 3D-ResNet was developed to randomly extract data in an 8:1:1 ratio for training, validating, and testing. We also collected external test data (40 with NTM-LD and 40 with MTB-LD) for external validation of the model. The activated region of interest was evaluated using a class activation map. The model was compared with three radiologists in the test set. RESULT: Patients with NTM-LD were older than those with MTB-LD, patients with MTB-LD had more cough, and those with NTM-LD had more dyspnoea, and the results were statistically significant (p < 0.05). The AUCs of our model on training, validating, and testing datasets were 0.90, 0.88, and 0.86, respectively, while the AUC on the external test set was 0.78. Additionally, the performance of the model was higher than that of the radiologist, and without manual labelling, the model automatically identified lung areas with abnormalities on CT > 1000 times more effectively than the radiologists. CONCLUSION: This study shows the efficacy of 3D-ResNet as a rapid auxiliary diagnostic tool for NTB-LD and MTB-LD. Its use can help provide timely and accurate treatment strategies to patients with these diseases.

16.
J Proteome Res ; 20(7): 3654-3663, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34110173

RESUMO

The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation. This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification. Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation). The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species. The site-specificity of N-glycans was revealed at the glycopeptide level by pGlyco software using different proteases. In total, 114 N-glycan compositions were identified from glycopeptide analysis. Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species. Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.


Assuntos
Eritropoetina , Espectrometria de Massas em Tandem , Cromatografia Líquida , Glicopeptídeos , Glicosilação , Polissacarídeos
18.
Front Pharmacol ; 12: 636213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867987

RESUMO

Resveratrol (RSV), a health-promoting natural product, has been shown to affect various cellular processes in tumor cells. However, the specific protein targets of RSV and the mechanism of action (MOA) of its anticancer effect remain elusive. In this study, the pharmacological activity of RSV was first evaluated in A549 cells, and the results showed that RSV significantly inhibited A549 cell migration but did not affect cell viability. To elucidate the underlying mechanism, a quantitative chemical proteomics approach was employed to identify the protein targets of RSV. A total of 38 target proteins were identified, and proteomic analysis showed that the targets were mainly involved in cytoskeletal remodeling and EMT, which were verified by subsequent in vitro and in vivo assays. In conclusion, RSV inhibits A549 cell migration by binding to multiple targets to regulate cytoskeletal remodeling and suppress EMT.

19.
Acta Biomater ; 127: 287-297, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33831570

RESUMO

Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared (NIR-I) window. However, their applications in the second near-infrared (NIR-II) window are still limited primarily due to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) is created as a molecularly engineered thiophene donor unit with high QYs to the redshift. Thiophene insertion initiates substantial redshifts of the absorbance as compared to its counterparts in which iodine is introduced. The fluorescent molecule can be triggered by an NIR laser with a single wavelength, thereby producing emission in the NIR-II windows. Single NIR laser-triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and the chemotherapeutic drug docetaxel (DTX) by using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen QY (ΦΔ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics. After intravenous administration of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor showed a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the combination of photodynamic therapy (PDT) and photothermic therapy (PTT). STATEMENT OF SIGNIFICANCE: The application of organic photosensitizers is still limited primarily due to low fluorescence quantum yields (QYs) in the second near-infrared (NIR-II) window. Here, a boron dipyrromethene (BDP) as a molecularly engineered thiophene donor unit with high QYs to the redshift is created. Phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and docetaxel (DTX) using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show high singlet oxygen QY (ΦΔ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics and a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the PDT/PTT combination therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Camundongos , Imagem Óptica , Fármacos Fotossensibilizantes/farmacologia , Tiofenos/farmacologia
20.
Int J Endocrinol ; 2021: 6616069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790965

RESUMO

COVID-19 is a kind of pneumonia with new coronavirus infection, and the risk of death in COVID-19 patients with diabetes is four times higher than that in healthy people. It is unclear whether there is a difference in chest CT images between type 2 diabetes mellitus (T2DM) and non-diabetes mellitus (NDM) COVID-19 patients. The aim of this study was to investigate the differences in chest CT images between T2DM and NDM patients with COVID-19 based on a quantitative method of artificial intelligence. A total of 62 patients with COVID-19 pneumonia were retrospectively enrolled and divided into group A (T2DM COVID-19 pneumonia group, n = 15) and group B (NDM COVID-19 pneumonia group, n = 47). The clinical and laboratory examination information of the two groups was collected. Quantitative features (volume of consolidation shadows and ground glass shadows, proportion of consolidation shadow (or ground glass shadow) to lobe volume, total volume, total proportion, and number) of chest spiral CT images were extracted using Dr. Wise @Pneumonia software. The results showed that among the 26 CT image features, the total volume and proportion of bilateral pulmonary consolidation shadow in group A were larger than those in group B (P=0.031 and 0.019, respectively); there was no significant difference in the total volume and proportion of bilateral pulmonary ground glass density shadow between the two groups (P > 0.05). In group A, the blood glucose level was correlated with the volume of consolidation shadow and the proportion of consolidation shadow to right middle lobe volume, and higher than those patients in group B. In conclusion, the inflammatory exudation in the lung of COVID-19 patients with diabetes is more serious than that of patients without diabetes based on the quantitative method of artificial intelligence. Moreover, the blood glucose level is positively correlated with pulmonary inflammatory exudation in COVID-19 patients.

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