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1.
Int J Nanomedicine ; 15: 483-495, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158206

RESUMO

Background: The complex preparation procedures and severe toxicities are two major obstacles facing the wide use of chimeric antigen receptor-modified T (CAR-T) cells in clinical cancer immunotherapy. The nanotechnology-based T cell temporary CAR modification may be a potential approach to solve these problems and make the CAR-T cell-based tumor therapy feasible and broadly applicable. Methods: A series of plasmid DNA-loaded self-assembled nanoparticles (pDNA@SNPsx/y) prepared from adamantane-grafted polyamidoamine (Ad-PAMAM) dendrimers of different generations (G1 or G5) and cyclodextrin-grafted branched polyethylenimine (CD-PEI) of different molecular weights (800, 2000, or 25,000 Da) were characterized and evaluated. The detailed physicochemical properties, cellular interaction, and cytotoxicity of selected pDNA@SNPG1/800 were systematically investigated. Thereafter, the epidermal growth factor receptor variant III (EGFRvIII) CAR-expression plasmid vector (pEGFRvIII-CAR) was constructed and encapsulated into SNPG1/800. The resulting pEGFRvIII-CAR@SNPG1/800 was used for Jurkat cell transient transfection, and the EGFRvIII-CAR expressed in transfected cells was measured by flow cytometry and Western blot. Finally, the response of EGFRvIII CAR-positive Jurkat T cell to target tumor cell was evaluated. Results: The pDNA@SNPG1/800 showed the highest efficacy in Jurkat cell gene transfection and exhibited low cytotoxicity. pEGFRvIII-CAR@SNPG1/800 can efficiently deliver pEGFRvIII-CAR into Jurkat T cells, thereby resulting in transient EGFRvIII-CAR expression in transfected cells. EGFRvIII-CAR that is present on the cell membrane enabled Jurkat T cells to recognize and bind specifically with EGFRvIII-positive tumor cells. Conclusion: These results indicated that pEGFRvIII-CAR@SNPG1/800 can effectively achieve T-cell transient CAR modification, thereby demonstrating considerable potential in CAR-T cancer therapy.

2.
J Clin Neurosci ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169364

RESUMO

The multifidus muscle morphology and its relation to the function of patients with degenerative lumbar spinal stenosis (DLSS) remains unclear. This study aimed to investigate the multifidus muscle morphology in patients with DLSS and to determine its relations to the patients function. Sixty-two patients with single-segment DLSS at L4-5 and sixty control patients with non-spinal-derived low back pain were retrospectively enrolled and further matched based on propensity scores. The Oswestry Disability Index (ODI) and bodily pain using the Short-Form Health Survey were evaluated. The cross-sectional area (CSA), CSA of fatty free (CSAF), and fatty infiltration rate [FIR; i.e., (1- CSAF/CSA) × 100%] of the multifidus muscle were measured on magnetic resonance images using ImageJ software. Adjustment for confounders was performed using generalized linear models. The FIR at L5-S1 in controls was statistically significant but slightly less than the DLSS group. The between-groups difference was 5% (p < 0.001), and 2.8% (p = 0.036) in the complete and matching cohorts, respectively, after adjustment. Statistically significant differences were not observed in other multifidus muscle parameters between the groups. FIR > 20% at L5-S1 was independently associated with ODI ≥ 41 in patients with DLSS [Retaining demography as control block or not, Odds ratio (OR) = 8.4, p = 0.023; OR = 12.3, p = 0.030]. The multifidus muscle at L5-S1 demonstrated slightly greater fatty infiltration in patients with L4-5 single-segment DLSS than controls. Significant fatty infiltration in the multifidus muscle at L5-S1 may be correlated with poor function in patients with L4-5 single-segment DLSS.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32115364

RESUMO

BACKGROUND: Antibody-mediated rejection (AMR) constitutes an important cause of cardiac allograft loss; however, all current therapeutic strategies represent systemic applications with unsatisfactory efficacy. Previously, we successfully non-invasively detected C4d, a specific marker for AMR diagnosis, in allografts using C4d-targeted microbubbles (MBC4d). In this study, we extended this approach by incorporating nitric oxide (NO), as high NO levels manifest immunosuppressive and anti-thrombotic effects. METHODS: We designed novel MBC4d loaded with NO (NO-MBC4d). A rat model of AMR was established by pre-sensitization with skin transplantation. Contrast-enhanced ultrasound (CEUS) images were obtained and quantitatively analyzed following NO-MBC4d injection. Allograft survival and histologic features were analyzed to evaluate the therapeutic effect and underlying mechanism of NO-MBC4d toward AMR. RESULTS: We successfully obtained CEUS images following NO-MBC4d injection and demonstrated that the ultrasound signal intensity of the myocardial area and clearance time of NO-MBC4d both increased with increased C4d grade, thereby realizing non-invasive diagnosis of AMR. Furthermore, allograft survival was significantly prolonged, and rejection was obviously attenuated following NO-MBC4d injection through significant suppression of thrombosis and reduction of inflammatory cell infiltrates. Overall, the therapeutic efficacy was significantly improved in the NO-MBC4d group compared with the control NO-MB group, demonstrating that precise treatment could significantly improve the therapeutic efficacy compared with that afforded by systemic applications. CONCLUSIONS: This study presented a novel tool to provide simultaneous non-invasive diagnosis and precise treatment of AMR using NO-MBC4d CEUS imaging, which may be expected to provide a better option for recipients with AMR in clinic.

4.
Nat Commun ; 11(1): 1259, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144239

RESUMO

The experimental discovery of Weyl semimetals offers unprecedented opportunities to study Weyl physics in condensed matters. Unique electromagnetic response of Weyl semimetals such as chiral magnetic effect has been observed and presented by the axial θ E · B term in electromagnetic Lagrangian (E and B are the electric and magnetic field, respectively). But till now, the experimental progress in this direction in Weyl semimetals is restricted to the DC regime. Here we report experimental access to the dynamic regime in Weyl semimetal NbAs by combining the internal deformation potential of coupled phonons with applied static magnetic field. While the dynamic E · B field is realized, it produces an anomalous phonon activity with a characteristic angle-dependence. Our results provide an effective approach to achieve the dynamic regime beyond the widely-investigated DC limit which enables the coupling between the Weyl fermions and the electromagnetic wave for further study of novel light-matter interactions in Weyl semimetals.

5.
J Antibiot (Tokyo) ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123311

RESUMO

Antibacterial peptides are a class of naturally occurring peptides produced by eukaryotes and prokaryotes. Some of them exhibit broad-spectrum antifungal activity. Antifungal peptides (AFPs) can be developed as antibiotic to control fungal infections in agriculture due to their different antifungal mechanisms. As actinomycetes are still one of the most important sources of novel antibiotics, in this review, the mechanisms of action of AFPs are explained. Characterization of several AFPs produced by actinomycetes and their biological activities against plant diseases are summarized. Furthermore, the pathway for total synthesis of naturally occurring cyclodepsipeptide, valinomycin, is proposed. Finally, the pathway for biosynthesis of kutzneride 2 is proposed and the structure-activity relationship of kutznerides is discussed.

6.
J Am Chem Soc ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32081011

RESUMO

Molecular oxygen resembles 3d and 4f metals in exhibiting long-range spin ordering and strong electron correlation behaviors in compounds. Ferromagnetic spin ordering and half-metallicity, however, are quite elusive and have not been well acknowledged. In this Article, we address this issue by studying how spins will interact with each other if the oxygen dimers are arranged in a different way from that in the known superoxides and peroxides by first-principles calculations. Based on the results of a structure search, thermodynamic studies, and lattice dynamics, we show that tetragonal α-BaNaO4 is a stable half-metal with a Curie temperature at 120 K, the first example in this class of compounds. Like 3d and 4f metals, the O2 dimer carries a local magnetic moment of 0.5 µB due to the unpaired electrons in its π* orbitals. This compound can be regarded as forming from the O2 dimer layers stacking in a head-to-head way. In contrast to the arrangement in AO2 (A = K, Rb, Cs), the spins are ferromagnetically coupled both within and between the layers. Spin polarization occurs in π* orbitals, with spin-up electrons fully occupying the valence band and spin-down electrons partially occupying the conduction band, forming semiconducting and metallic channels, respectively. Our results highlight the importance of geometric arrangement of O2 dimers in inducing ferromagnetism and other novel properties in O2-dimer-containing compounds.

7.
Sci Adv ; 6(7): eaay6134, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32110733

RESUMO

Thin-film black phosphorus (BP) is an attractive material for mid-infrared optoelectronic applications because of its layered nature and a moderate bandgap of around 300 meV. Previous photoconduction demonstrations show that a vertical electric field can effectively reduce the bandgap of thin-film BP, expanding the device operational wavelength range in mid-infrared. Here, we report the widely tunable mid-infrared light emission from a hexagonal boron nitride (hBN)/BP/hBN heterostructure device. With a moderate displacement field up to 0.48 V/nm, the photoluminescence (PL) peak from a ~20-layer BP flake is continuously tuned from 3.7 to 7.7 µm, spanning 4 µm in mid-infrared. The PL emission remains perfectly linear-polarized along the armchair direction regardless of the bias field. Moreover, together with theoretical analysis, we show that the radiative decay probably dominates over other nonradiative decay channels in the PL experiments. Our results reveal the great potential of thin-film BP in future widely tunable, mid-infrared light-emitting and lasing applications.

8.
ACS Nano ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31922387

RESUMO

Having a sizable band gap and high carrier mobility, black phosphorus (BP) is a promising two-dimensional material for high-frequency electronic and optoelectronic devices. Further, for metal-oxide-semiconductor field-effect transistors (MOSFETs) operating at high frequencies, they must have a top gate of submicron length instead of the commonly used global back gate. However, without the global back gate to electrostatically induce doping in BP, top-gated submicron BP MOSFETs have not reached their full potential mainly due to large contact resistances. Here, we report top-gated submicron BP MOSFETs with local contact bias electrodes to induce doping in the contact region. This resulted in reduced contact resistance and, in turn, orders of magnitude improvement in current capacity (>500 µA/µm) and peak transconductance (>40 µS/µm), if compared with top-gated BP transistors without any back-gating scheme. In turn, these improvements resulted in a forward current gain cutoff frequency of 37 GHz and a maximum frequency of oscillation of 22 GHz at room temperature, the highest reported for BP MOSFETs up to date.

9.
J Med Chem ; 63(3): 1132-1141, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31927997

RESUMO

Precise regulation of membrane-active peptide activity is a frontier of research to facilitate its applicational translation. A clear understanding of how a peptide's physicochemical properties determine its mode of action (MOA) will aid the process. Herein, anionic glutamate residue-based scanning was applied to the hydrophobic surface of a self-assembling lysine-rich cationic amphipathic peptide (CAP) KL1. Single-site mutations from leucine to glutamate dramatically changed the MOA of all mutants from membranolytic to nonlytic. An apoptosis-inducing mutant L2E unable to self-assemble under extracellular anions exhibited a different conformational transformation process in the amphiphilic environment than KL1. Further adjustment of the overall positive charge allowed regulation of cytotoxic potency without affecting the MOA determined by the lack of preassembly formation. Compared with KL1, hemolytic toxicities of nonmembranolytic peptides were greatly reduced, with safety indices increased. This work thus provided novel insights into and integrated rationales on the improvement of CAPs for both anticancer activity and safety profile.

10.
Appl Microbiol Biotechnol ; 104(5): 2229-2241, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31915903

RESUMO

The aquatic microbial community is sensitive to environmental change; however, the impacts of those changes combined with disease outbreaks affecting S. paramamosain are unknown. Thus, from March to October, we explored the interaction between aquacultural environmental conditions and microbial composition and function in open-air aquaculture ponds containing S. paramamosain in Southern China. The microbial community structure was significantly positively correlated with microbial community function. The environment variables such as temperature and salinity during May and June changed more quickly compared with other periods, resulting changes in the structure and function of the microbial community affected S. paramamosain survivability, with higher crab mortality observed from May to June compared with other periods. These included changes in the relative abundance of Microtrichales, Synechococcales, Rhodobacterales, Chitinophagales, and SAR11_clade, and corresponding functions associated with glycolysis and/or gluconeogenesis, porphyrin and chlorophyll metabolism, photosynthetic proteins, and transcription factors. These changes could impact S. paramamosain mortality and be used to evaluate the health status of the ponds. Though the environment variables during July~October changed slowly comparing to May and June, the ponds microflora changed which benefit S. paramamosain survivability with correspondingly low S. paramamosain mortality. Therefore, rapid environmental change alters the structure and function of the aquatic microflora, increasing S. paramamosain mortality.


Assuntos
Braquiúros/fisiologia , Microbiota , Tanques/microbiologia , Microbiologia da Água , Animais , Aquicultura , China , Monitoramento Ambiental , Microbiota/genética , Nutrientes/análise , Tanques/química , Salinidade , Estações do Ano , Temperatura Ambiente
11.
Artigo em Inglês | MEDLINE | ID: mdl-31683012

RESUMO

The mud crab, Scylla paramamosain, is an economically-important crab in China. Air exposure is an important environmental stressor during mud crab culture and transportation. Adaptive mechanisms responding to air exposure in mud crabs are still poorly understood. In this study, mud crabs were exposed to air for 120 h. Air exposure decreased total hemocyte counts, led to cytological damage, and caused high mortality. Transcriptomic analysis was conducted at 0, 6 and 96 h after air exposure. A total of 3530 differentially expressed genes (DEGs) were identified. DEGs were mainly involved in the oxidative stress response, metabolism, cellular processes, signal transduction, and immune functions. Transcriptomic analysis also revealed that genes of glycolysis and of the tricarboxylic acid cycle were key factors in regulating the mud crab adaptation to air exposure.

12.
World J Surg ; 44(1): 213-222, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31637507

RESUMO

BACKGROUND: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. METHODS: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X-tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. RESULTS: Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C-index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. CONCLUSIONS: Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31760077

RESUMO

Glutathione peroxidases (GPx) are parts of the enzymatic antioxidant system that can eliminate the peroxides produced as effect of reactions of molecules with reactive oxygen species (ROS). In this study, a selenium-dependent glutathione peroxidase 3 cDNAs (designated as SpGPx3) was obtained from the mud crab Scylla paramamosain. The open reading frame (ORF) of SpGPx3 was 639 bp, which encoded a putative protein of 212 amino acids. SpGPx3 protein contained a characteristic GPx signature motif, and an active site motif. Mud crabs were exposed to 20 mg L-1 nitrite for 72 h. Quantitative real-time PCR analysis revealed that the SpGPx3 mRNA was distributed abundantly in mud crab. The transcript levels of antioxidant enzyme genes (SpGPx3, SpSOD and SpCAT) were obviously induced after acute nitrite exposure. After knockdown of the SpGPx3 level, the mortality of mud crabs and malondialdehyde (MDA) content significantly increased under nitrite stress. These results suggested that SpGPx3 played an important role in protecting organisms against oxidative stress.

14.
Life Sci ; 241: 117146, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31816325

RESUMO

AIMS: Diabetic retinopathy (DR) is the main cause of blindness in adults and investigating new therapeutic targets for DR is necessary. This study aimed to investigate the effect of high-mobility group box 1 (HMGB1) protein and its mechanism in diabetic retinopathy (DR) were investigated. MAIN METHODS: Human retinal endothelial cells (HREC) were uesd for chip-seq. Sprague Dawley (SD) rats were randomly divided into control group, HMGB1 group, diabetes mellitus (DM) combined with HMGB1 siRNA group, and DM group. Next, eyeballs were removed and retinas were detached for western blot. The DM model of cell was built by increasing the glucose concentration in cell culture medium. The regulation of HMGB1 was achieved by short hairpin (sh)-HMGB1 transfection, then, the transfected cells were harvested for luciferase assay, western blot and qRT-PCR analyses as well as proliferation and apoptosis detection. KEY FINDINGS: Chip-seq and luciferase assay showed the possible transcription factor functions of HMGB1 and IKB-α was one of the HMGB1 binding sites. In vivo and in vitro results indicated high expression of HMGB1 and NF-kB and low expression of IKB-α in DR and the expression of IKB-α and NF-kB was regulated by HMGB1. Moreover, cell assays showed that HMGB1 inhibited cell proliferation and promoted apoptosis. SIGNIFICANCE: The results from the present study showed that HMGB1 may be involved in the pathogenesis of DR as a transcription factor through NF-kB pathway. Therefore, blockade of HMGB1 may be a new method for the treatment of DR.


Assuntos
Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Proteína HMGB1/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Proteína HMGB1/genética , Humanos , Masculino , Inibidor de NF-kappaB alfa/genética , NF-kappa B/genética , Ratos , Ratos Sprague-Dawley , Retina/citologia , Retina/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-31654827

RESUMO

Glutathione S-transferase (GST) plays important roles in cellular detoxification and antioxidant defense. A Mu-type glutathione S-transferase (designated as SpMu-GST) was obtained from the mud crab Scylla paramamosain. The open reading frame of SpMu-GST was comprised a 690 bp, which encoded a putative protein of 229 amino acids. Quantitative real-time PCR (qRT-PCR) revealed that the SpMu-GST mRNA was expressed in all examined tissues, with highest expression in hepatopancreas. During ammonia exposure, the SpMu-GST transcriptions in hepatopancreas and gill were significantly up-regulated at early exposure time. Moreover, RNA interference (RNAi) experiment was designed to understand the roles of SpMu-GST under ammonia exposure. Ammonia exposure reduced the levels of glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and total antioxidative capacity (T-AOC), and increased the formation of malondialdehyde (MDA). After knockdown of the SpMu-GST level, GST activity and T-AOC were significantly decreased at some exposure time after ammonia exposure. However, the mortality of mud crabs and malondialdehyde (MDA) contents significantly increased under ammonia exposure. These results further suggested that SpMu-GST played a critical role in mud crab antioxidant defenses in response to environmental stress.


Assuntos
Amônia/toxicidade , Braquiúros/enzimologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/classificação , Animais , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/enzimologia , Hepatopâncreas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Estresse Fisiológico/efeitos dos fármacos
16.
J Environ Manage ; 253: 109636, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678688

RESUMO

Dibutyl phthalate (DBP) is a frequently detected farmland contaminant that is harmful to the environment and human health. In this study, a DBP-degrading endophytic Bacillus siamensis strain T7 was immobilized in rice husk-derived biochar for bioremediation of DBP-polluted agricultural soils. The effects of this microbe-biochar composite on the soil prokaryotic community and the mechanism by which it regulates DBP degradation, were also investigated. A supplement of T7-biochar composite not only significantly boosted DBP biodegradation in soil by raising the DBP degradation rate constant and half-life from 0.1979 d-1 and 2.3131 d to 0.2434 d-1 and 2.1062 d, respectively, but also impeded DBP uptake by leafy vegetables. The general bioremediation effect of T7-biochar alliance excelled pure T7 suspensions and biochar, by trapping more DBP and boosting its complete degradation in soil. Besides, the combination of strain T7 and biochar can increase the proportion of some beneficial bacteria and boost the functional diversity of soil prokaryotic community, then to a certain extent may reverse the negative effect of DBP pollution on the agricultural soils. These results indicate that the rice-husk-derived biochar is a proper media when utilizing functional microbes into environmental treatment. Overall, T7-biochar composite is a promising soil modifier for soil bioremediation and the production of DBP-free crops.


Assuntos
Bacillus , Poluentes do Solo , Biodegradação Ambiental , Carvão Vegetal , Dibutilftalato , Humanos , Solo , Verduras
17.
Chemosphere ; 239: 124668, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31494325

RESUMO

Nitrite is one of major environmental pollutants that can impact immunological parameters in aquatic organisms. In the present study, we investigated the effects of nitrite exposure on oxidative stress, DNA damage and apoptosis in mud crab (Scylla paramamosain). Mud crab were exposed to 0, 5, 10 and 15 mg L-1 nitrite for 72 h. These data showed that acid phosphatase (ACP) and alkaline phosphatase (ALP) activity significantly decreased in treatments with various concentrations of nitrite (5, 10 and 15 mg L-1) after 24 and 48 h, while the levels of nitric oxide (NO) significantly increased in these treatments. Nitrite exposure could suppress superoxide dismutase (SOD) and catalase (CAT) activity, and increase the formation of malondialdehyde (MDA) after 48 and 72 h of exposure. In addition, nitrite exposure decreased total haemocyte counts after 48 and 72 h of exposure. Cytological damage, DNA damage and apoptosis was observed obviously at 72 h after nitrite exposure. Moreover, nitrite exposure significantly induced the mRNA levels of phosphorylated Jun N-terminal kinases (JNK), and eventually activated p53 signaling and caspase-3. These results indicated that nitrite exposure could induce oxidative stress, which further caused DNA damage and apoptosis in mud crab. Our results will be helpful to understand the mechanism of nitrite toxicity on crustaceans.


Assuntos
Apoptose/efeitos dos fármacos , Braquiúros/efeitos dos fármacos , Dano ao DNA/genética , Nitritos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Braquiúros/genética , Catalase/metabolismo , Hemócitos , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo
18.
Onco Targets Ther ; 12: 9201-9213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807004

RESUMO

Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with high incidence. The underlying molecular mechanisms of HCC development have been intensively studied. CLK3 (CDC Like Kinase 3) is a nuclear dual-specificity kinase and regulates gene splicing. We investigated the expression profile and functional role of CLK3 in HCC. Methods: Immunohistochemistry (IHC) and Western blot were performed to determine CLK3 expression in HCC tissues. Bioinformatics analysis using TCGA and GEO database was conducted to evaluate the relationship between CLK3 expression and HCC prognosis. Cell proliferation was assessed by CCK8, EdU and colony formation assays, while transwell and wound-healing assays were performed to investigate the cell migration and invasion in vitro. Xenograft nude mouse model was used to test the function of CLK3 on tumor growth in vivo. Luciferase reporter assay, Western blot and RT-qPCR were conducted to verify the miRNA that directly targeted CLK3. Results: CLK3 was markedly upregulated in HCC tissues, and the expression levels of CLK3 were closely associated with TNM stages and HCC prognosis. Functional analysis indicated that knockdown of CLK3 could suppress HCC cell growth, invasion and migration in vitro, and inhibit tumor development in vivo. Moreover, CLK3 was demonstrated as a direct target of miR-144 and miR-144 expression was inversely correlated with CLK3 expression in HCC. Enforced overexpression of miR-144 markedly inhibited the CLK3 expression while overexpression of CLK3 partially reversed the inhibitory function of miR-144 on HCC cell growth and metastasis. Mechanistically, we found that miR-144 overexpression inhibited Wnt/ß-catenin signaling and the inhibition could be partly abolished by overexpression of CLK3. Conclusion: In summary, we demonstrate tumor suppressor miR-144 suppresses hepatocellular carcinoma development and metastasis via regulating CLK3 and Wnt/ß-catenin signaling, indicating that miR-144/CLK3 could be used for HCC diagnosis and treatment.

19.
Med Phys ; 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31837239

RESUMO

PURPOSE: To train deep learning models to differentiate benign and malignant breast tumors in ultrasound images, we need to collect many training samples with clear labels. In general, biopsy results can be used as benign/malignant labels. However, most clinical samples generally do not have biopsy results. Previous works have proposed generating benign/malignant labels according to Breast Imaging, Reporting and Data System (BI-RADS) ratings. However, this approach will cause noisy labels, which means that the benign/malignant labels produced from BI-RADS diagnoses may be inconsistent with the ground truths. Consequently, deep models will overfit the noisy labels and hence obtain poor generalization performance. In this work, we mainly focus on how to reduce the negative effect of noisy labels when they are used to train breast tumor classification models. METHODS: We propose an effective approach called noise filter network (NF-Net) to address the problem of noisy labels when training breast tumor classification models. Specifically, to prevent deep models from overfitting the noisy labels, we propose incorporating two softmax layers for classification. Additionally, to strengthen the effect of clean labels, we design a teacher-student module for distilling the knowledge of clean labels. RESULTS: We conduct extensive comparisons with the existing works on addressing noisy labels. Our method achieves a classification accuracy of 73%, with a precision of 69%, recall of 80%, and F1-score of 0.74. This result is significantly better than those of the existing state-of-the-art works on addressing noisy labels. CONCLUSIONS: This work provides a means to overcome the label shortage problem in training breast tumor classification models. Specifically, we can generate benign/malignant labels according to the BI-RADS ratings. Although this approach will cause noisy labels, the design of NF-Net can effectively reduce the negative effect of such labels.

20.
Opt Express ; 27(26): 37771-37780, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31878552

RESUMO

Recently, a type of curved light beams, photonic hooks (PHs), was theoretically predicted and experimentally observed. The production of photonic hook (PH) is due to the breaking of structural symmetry of a plane-wave illuminated microparticle. Herein, we presented and implemented a new approach of utilizing the symmetry-broken of the microparticles in material composition for the generation of PHs from Janus microcylinders. Finite element method-based numerical simulation and energy flow-represented theoretical analysis were used to investigate the field distribution characteristics and formation mechanism of the PHs. The full width at half-maximum (FWHM) of the PH (∼0.29λ) is smaller than the FWHM of the photonic nanojet (∼0.35λ) formed from a circular microcylinder with the same geometric radius. By changing the refractive index contrasts between upper and lower half-cylinders or rotating the Janus microcylinder relative to the central axis, the shape profiles of the PHs can be efficiently modulated. The tunability of the PHs through simple stretching or compression operations for the Janus microcylinder constituted by one solid inorganic half-cylinder and the other flexible polymer half-cylinder was studied and discussed as well.

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