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1.
Opt Express ; 32(10): 17295-17317, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858917

RESUMO

To achieve defect detection in bare polycrystalline silicon solar cells under electroluminescence (EL) conditions, we have proposed ASDD-Net, a deep learning algorithm evaluated offline on EL images. The model integrates strategies such as downsampling adjustment, feature fusion optimization, and detection head improvement. The ASDD-Net utilizes the Space to Depth (SPD) module to effectively extract edge and fine-grained information. The proposed Enhanced Cross-Stage Partial Network Fusion (EC2f) and Hybrid Attention CSP Net (HAC3) modules are placed at different positions to enhance feature extraction capability and improve feature fusion effects, thereby enhancing the model's ability to perceive defects of different sizes and shapes. Furthermore, placing the MobileViT_CA module before the second detection head balances global and local information perception, further enhancing the performance of the detection heads. The experimental results show that the ASDD-Net model achieves a mAP value of 88.81% on the publicly available PVEL-AD dataset, and the detection performance is better than the current SOTA model. The experimental results on the ELPV and NEU-DET datasets verify that the model has some generalization ability. Moreover, the proposed model achieves a processing frame rate of 69 frames per second, meeting the real-time defect detection requirements for solar cell surface defects.

2.
Bioorg Chem ; 142: 106952, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37952486

RESUMO

PARP1 is a multifaceted component of DNA repair and chromatin remodeling, making it an effective therapeutic target for cancer therapy. The recently reported proteolytic targeting chimera (PROTAC) could effectively degrade PARP1 through the ubiquitin-proteasome pathway, expanding the therapeutic application of PARP1 blocking. In this study, a series of nitrogen heterocyclic PROTACs were designed and synthesized through ternary complex simulation analysis based on our previous work. Our efforts have resulted in a potent PARP1 degrader D6 (DC50 = 25.23 nM) with high selectivity due to nitrogen heterocyclic linker generating multiple interactions with the PARP1-CRBN PPI surface, specifically. Moreover, D6 exhibited strong cytotoxicity to triple negative breast cancer cell line MDA-MB-231 (IC50 = 1.04 µM). And the proteomic results showed that the antitumor mechanism of D6 was found that intensifies DNA damage by intercepting the CDC25C-CDK1 axis to halt cell cycle transition in triple-negative breast cancer cells. Furthermore, in vivo study, D6 showed a promising PK property with moderate oral absorption activity. And D6 could effectively inhibit tumor growth (TGI rate = 71.4 % at 40 mg/kg) without other signs of toxicity in MDA-MB-321 tumor-bearing mice. In summary, we have identified an original scaffold and potent PARP1 PROTAC that provided a novel intervention strategy for the treatment of triple-negative breast cancer.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Neoplasias de Mama Triplo Negativas/patologia , Proteômica , Proliferação de Células , Pontos de Checagem do Ciclo Celular , Nitrogênio , Linhagem Celular Tumoral , Fosfatases cdc25 , Poli(ADP-Ribose) Polimerase-1 , Proteína Quinase CDC2
3.
Inorg Chem ; 62(11): 4705-4715, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36880867

RESUMO

The low efficient transfer of photogenerated electrons to an active catalytic site is a pivotal problem for the photoreduction of highly soluble hexavalent uranium [U(VI)] to low soluble tetravalent uranium [U(IV)]. Herein, we successfully synthesized a TiO2-x/1T-MoS2/reduced graphene oxide heterojunction (T2-xTMR) with dual charge-transfer channels by exploiting the difference in Fermi levels between the heterojunction interfaces, which induced multilevel separation of photogenerated carriers. Theoretical and experimental results demonstrate that the presence of the electron buffer layer promoted the efficient migration of photogenerated electrons between the dual charge-transfer channels, which achieved effective separation of photogenerated carriers in physical/spatial dimensions and significantly extended the lifetime of photogenerated electrons. The migration of photogenerated electrons to the active catalytic site after multilevel spatial separation enabled the T2-xTMR dual co-photocatalyst to remove 97.4% of the high concentration of U(VI) from the liquid-phase system within 80 min. This work provides a practical reference for utilizing multiple co-catalysts to accomplish directed spatial separation of photogenerated carriers.

4.
Small ; 18(17): e2107951, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35355404

RESUMO

Silica glasses have wide applications in industrial fields due to their extraordinary properties, such as high transparency, low thermal expansion coefficient, and high hardness. However, current methods of fabricating silica glass generally require long thermal treatment time (up to hours) and complex setups, leading to high cost and slow manufacturing speed. Herein, to obtain high-quality glasses using a facile and rapid method, an ultrafast high-temperature sintering (UHS) technique is reported that requires no additional pressure. Using UHS, silica precursors can be densified in seconds due to the large heating rate (up to 102 K s-1 ) of closely placed carbon heaters. The typical sintering time is as short as ≈10 s, ≈1-3 orders of magnitude faster than other methods. The sintered glasses exhibit relative densities of > 98% and high visible transmittances of ≈90%. The powder-based sintering process also allows rapid doping of metal ions to fabricate colored glasses. The UHS is further extended to sinter other functional glasses such as indium tin oxide (ITO)-doped silica glass, and other transparent ceramics such as Gd-doped yttrium aluminum garnet. This study demonstrates an UHS proof-of-concept for the rapid fabrication of high-quality glass and opens an avenue toward rapid discovery of transparent materials.

5.
J Transl Med ; 20(1): 217, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562811

RESUMO

BACKGROUND: The two oncogenic human gammaherpesviruses, Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), both downregulate immune surface molecules, such as MHC-I, ICAM-1, and B7-2, enabling them to evade T-cell and natural killer cell immunity. Both also either encode for human cyclin homologues or promote cellular cyclin activity, and this has been shown to be important for proliferation and survival of gammaherpesvirus-induced tumors. CDK4/6 inhibitors, which are approved for certain breast cancers, have been shown to enhance expression of MHC-I in cell lines and murine models of breast cancer, and this was attributed to activation of interferons by endogenous retrovirus elements. However, it was not known if this would occur in gammaherpesvirus-induced tumors in which interferons are already activated. METHODS: Multiple KSHV/EBV-infected cell lines were treated with CDK4/6 inhibitors. The growth of viable cells and expression of surface markers was assessed. T cell activation stimulated by the treated cells was assayed by a T-cell activation bioassay. Both viral and host gene expression was surveyed using RT-qPCR. RESULTS: Three CDK4/6 inhibitors, abemaciclib, palbociclib, and ribociclib, inhibited cell growth in KSHV-induced primary effusion lymphoma (PEL) and EBV positive Burkitt's lymphoma (BL) cell lines, and KSHV-infected human umbilical vein endothelial cells (HUVECs). Moreover, CDK4/6 inhibitors increased mRNA and surface expression of MHC-I in all three and prevented downregulation of MHC-I surface expression during lytic replication in KSHV-infected cells. CDK4/6 inhibitors also variably increased mRNA and surface expression of ICAM-1 and B7-2 in the tested lines. Abemaciclib also significantly enhanced T-cell activation induced by treated PEL and BL cells. Certain gammaherpesvirus genes as well as endogenous retrovirus (ERV) 3-1 genes were enhanced by CDK4/6 inhibitors in most PEL and BL lines and this enhancement was associated with expression of gamma interferon-induced genes including MHC-I. CONCLUSIONS: These observations provide evidence that CDK4/6 inhibitors can induce expression of surface immune markers MHC-I, B7-2, and ICAM-1 in gammaherpesvirus-infected cell lines and induce virus-specific immunity. They can thus thwart virus-induced immune evasion. These effects, along with their direct effects on KSHV- or EBV-induced tumors, provide a rational for the clinical testing of these drugs in these tumors.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 8 , Neoplasias , Animais , Morte Celular , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Ciclinas , Células Endoteliais , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/fisiologia , Herpesvirus Humano 8/fisiologia , Humanos , Molécula 1 de Adesão Intercelular , Interferons , Neoplasias/complicações , RNA Mensageiro , Linfócitos T
6.
BMC Anesthesiol ; 22(1): 176, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672660

RESUMO

BACKGROUND: To study the respective peripheral and systemic mechanisms of action of dexmedetomidine, as adjuvant to regional anesthesia, we compared dexmedetomidine added to ropivacaine for mid-forearm nerve blocks, to either systemic-only dexmedetomidine, and to a control with no dexmedetomidine. METHODS: Sixty patients undergoing hand surgery were randomly divided into three groups (n = 20 per group). Each group underwent a triple-nerve (median, radial and ulnar) mid-forearm blocks with 0.75% ropivacaine. In the DexP group, 60 µg of dexmedetomidine were added to the anesthetic mixture, while in the DexIV group, they were intravenously infused. Normal saline as a placebo was used, either as adjuvant, or intravenously. All patients underwent also a supraclavicular block with 1.5% lidocaine for tourniquet pain. The main outcomes were the duration of analgesia and the duration of sensory blockade separately for each nerve termination of the upper limb, and the duration of motor blockade of the upper limb. Tolerance was assessed by blood pressure and heart rate, and the report of adverse events. RESULTS: Duration of analgesia was longer in the DexP group, in comparison to the two other groups (P < 0.001), while it was similar in the DexIV and the control group. For cutaneous territories targeted by the three mid-forearm blocks, the between-group differences behaved similarly. For the other cutaneous territories (musculocutaneous and posterior brachial cutaneous nerves), duration of sensory blockade was shorter in the control group than in the two dexmedetomidine groups. For duration of motor blockade, the between-group differences behaved similarly. Both blood pressure and heart rate were reduced in the DexP and the DexIV groups, compared to the control. CONCLUSIONS: Dexmedetomidine used as an adjuvant to regional anesthesia may act mostly though a perineural mechanism, especially for the sensory aspects of anesthesia. A systemic action might however explain other clinical effects. TRIAL REGISTRATION: ChiCTR-IOR-17011149 , date of registration: 16/04/2017.


Assuntos
Bloqueio do Plexo Braquial , Dexmedetomidina , Anestésicos Locais , Humanos , Estudos Prospectivos , Ropivacaina
7.
Sensors (Basel) ; 20(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32751868

RESUMO

Remote sensing targets have different dimensions, and they have the characteristics of dense distribution and a complex background. This makes remote sensing target detection difficult. With the aim at detecting remote sensing targets at different scales, a new You Only Look Once (YOLO)-V3-based model was proposed. YOLO-V3 is a new version of YOLO. Aiming at the defect of poor performance of YOLO-V3 in detecting remote sensing targets, we adopted DenseNet (Densely Connected Network) to enhance feature extraction capability. Moreover, the detection scales were increased to four based on the original YOLO-V3. The experiment on RSOD (Remote Sensing Object Detection) dataset and UCS-AOD (Dataset of Object Detection in Aerial Images) dataset showed that our approach performed better than Faster-RCNN, SSD (Single Shot Multibox Detector), YOLO-V3, and YOLO-V3 tiny in terms of accuracy. Compared with original YOLO-V3, the mAP (mean Average Precision) of our approach increased from 77.10% to 88.73% in the RSOD dataset. In particular, the mAP of detecting targets like aircrafts, which are mainly made up of small targets increased by 12.12%. In addition, the detection speed was not significantly reduced. Generally speaking, our approach achieved higher accuracy and gave considerations to real-time performance simultaneously for remote sensing target detection.

8.
Sensors (Basel) ; 21(1)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33379344

RESUMO

Target detection in hyperspectral imagery (HSI) aims at extracting target components of interest from hundreds of narrow contiguous spectral bands, where the prior target information plays a vital role. However, the limitation of the previous methods is that only single-layer detection is carried out, which is not sufficient to discriminate the target parts from complex background spectra accurately. In this paper, we introduce a hierarchical structure to the traditional algorithm matched filter (MF). Because of the advantages of MF in target separation performance, that is, the background components are suppressed while preserving the targets, the detection result of MF is used to further suppress the background components in a cyclic iterative manner. In each iteration, the average output of the previous iteration is used as a suppression criterion to distinguish these pixels judged as backgrounds in the current iteration. To better stand out the target spectra from the background clutter, HSI spectral input and the given target spectrum are whitened and then used to construct the MF in the current iteration. Finally, we provide the corresponding proofs for the convergence of the output and suppression criterion. Experimental results on three classical hyperspectral datasets confirm that the proposed method performs better than some traditional and recently proposed methods.

9.
PLoS Pathog ; 13(4): e1006281, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28403202

RESUMO

Herpesvirus gH/gL envelope glycoprotein complexes are key players in virus entry as ligands for host cell receptors and by promoting fusion of viral envelopes with cellular membranes. Human cytomegalovirus (HCMV) has two alternative gH/gL complexes, gH/gL/gO and gH/gL/UL128,130,131A which both shape the HCMV tropism. By studying binding of HCMV particles to fibroblasts, we could for the first time show that virion gH/gL/gO binds to platelet-derived growth factor-α (PDGFR-α) on the surface of fibroblasts and that gH/gL/gO either directly or indirectly recruits gB to this complex. PDGFR-α functions as an entry receptor for HCMV expressing gH/gL/gO, but not for HCMV mutants lacking the gH/gL/gO complex. PDGFR-α-dependent entry is not dependent on activation of PDGFR-α. We could also show that the gH/gL/gO-PDGFR-α interaction starts the predominant entry pathway for infection of fibroblasts with free virus. Cell-associated virus spread is either driven by gH/gL/gO interacting with PDGFR-α or by the gH/gL/UL128,130,131A complex. PDGFR-α-positive cells may thus be preferred first target cells for infections with free virus which might have implications for the design of future HCMV vaccines or anti-HCMV drugs.


Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/fisiologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas do Envelope Viral/metabolismo , Internalização do Vírus , Linhagem Celular , Células Cultivadas , Citomegalovirus/genética , Fibroblastos/virologia , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Complexos Multiproteicos , Mutação , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Proteínas Recombinantes , Proteínas do Envelope Viral/genética , Vírion
10.
PLoS Pathog ; 11(2): e1004640, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25659098

RESUMO

Herpesviruses form different gH/gL virion envelope glycoprotein complexes that serve as entry complexes for mediating viral cell-type tropism in vitro; their roles in vivo, however, remained speculative and can be addressed experimentally only in animal models. For murine cytomegalovirus two alternative gH/gL complexes, gH/gL/gO and gH/gL/MCK-2, have been identified. A limitation of studies on viral tropism in vivo has been the difficulty in distinguishing between infection initiation by viral entry into first-hit target cells and subsequent cell-to-cell spread within tissues. As a new strategy to dissect these two events, we used a gO-transcomplemented ΔgO mutant for providing the gH/gL/gO complex selectively for the initial entry step, while progeny virions lack gO in subsequent rounds of infection. Whereas gH/gL/gO proved to be critical for establishing infection by efficient entry into diverse cell types, including liver macrophages, endothelial cells, and hepatocytes, it was dispensable for intra-tissue spread. Notably, the salivary glands, the source of virus for host-to-host transmission, represent an exception in that entry into virus-producing cells did not strictly depend on either the gH/gL/gO or the gH/gL/MCK-2 complex. Only if both complexes were absent in gO and MCK-2 double-knockout virus, in vivo infection was abolished at all sites.


Assuntos
Infecções por Citomegalovirus/transmissão , Citomegalovirus/fisiologia , Glicoproteínas de Membrana/metabolismo , Proteínas do Envelope Viral/metabolismo , Tropismo Viral/fisiologia , Animais , Infecções por Citomegalovirus/metabolismo , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Endogâmicos BALB C
11.
Sci Technol Adv Mater ; 17(1): 200-209, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27877870

RESUMO

CuAlO2 has been examined as a potential luminescent material by substituting Eu for Al cations in the delafossite structure. CuAlO2:Eu3+ nanofibers have been prepared via electrospinning for the ease of mitigating synthesis requirements and for future optoelectronics and emerging applications. Single-phase CuAlO2 fibers could be obtained at a temperature of 1100 °C in air. The Eu was successfully doped in the delafossite structure and two strong emission bands at ~405 and 610 nm were observed in the photoluminescence spectra. These bands are due to the intrinsic near-band-edge transition of CuAlO2 and the f-f transition of the Eu3+ activator, respectively. Further electrical characterization indicated that these fibers exhibit semiconducting behavior and the introduction of Eu could act as band-edge modifiers, thus changing the thermal activation energies. In light of this study, CuAlO2:Eu3+ fibers with both strong photoluminescence and p-type conductivity could be produced by tailoring the rare earth doping concentrations.

12.
BMC Anesthesiol ; 15: 66, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25924894

RESUMO

BACKGROUND: Epinephrine is a first-line drug for cardiopulmonary resuscitation, but its efficacy in the treatment of bupivacaine-induced cardiac toxicity is still in question. We hypothesized that epinephrine can reverse cardiac inhibition of bupivacaine by modulating ion flows through the ventricular myocyte membrane channels of rats. The aim of this study was to observe and report the effects of epinephrine on high-concentration bupivacaine-induced inhibition of sodium (INa), L-type calcium (ICa-L), and transient outward potassium (Ito) currents in the ventricular myocytes of rats. METHODS: The ventricular myocytes were isolated from Sprague-Dawley rats (250-300 g) by acute enzymatic dissociation. The whole-cell patch clamp technique was used to record the ion channel currents in single ventricular myocytes both before and after administration of medications. RESULT: Administration of bupivacaine 100 µmol/L significantly reduced INa, (P < 0.05). However, administration of bupivacaine 100 µmol/L in conjunction with epinephrine 0.15 µg/ml had no effect in restoring INa to its previous state. Similarly, a sharp decline of ICa-L and Ito was observed after administration of bupivacaine 100 µmol/L (P < 0.05). In contrast to INa, ICa-L and Ito were significantly improved after the administration of the aforementioned combination of bupivacaine and epinephrine (P < 0.05). CONCLUSION: Epinephrine can reverse high-concentration bupivacaine induced inhibition of ICa-L and Ito, but not INa. Thus, epinephrine's effectiveness in reversal of bupivacaine-induced cardiac toxicity secondary to sodium channel inhibition may be limited.


Assuntos
Anestésicos Locais/farmacologia , Bupivacaína/farmacologia , Canais de Cálcio Tipo L/efeitos dos fármacos , Epinefrina/farmacologia , Canais de Potássio/efeitos dos fármacos , Canais de Sódio/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Animais , Bupivacaína/administração & dosagem , Bloqueadores dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ventrículos do Coração/citologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Ratos Sprague-Dawley , Bloqueadores dos Canais de Sódio/farmacologia
13.
J Cardiothorac Vasc Anesth ; 29(6): 1550-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26409920

RESUMO

OBJECTIVE: To compare paravertebral block under thoracoscopy with wound infiltration at an early stage after video-assisted thoracic lobectomy surgery. DESIGN: A prospective, randomized, triple-blinded, placebo-controlled trial. SETTING: A single-center university hospital. PARTICIPANTS: Patients scheduled for video-assisted thoracic lobectomy surgery between February 20, 2014 and June 1, 2014 randomly were allocated into paravertebral block (PVB) (n = 35) and infiltration (n = 35) groups. INTERVENTIONS: In the PVB group, 0.5% ropivacaine was injected into the paravertebral space by the surgeon under direct vision with placebo infiltration of saline in the wounds. In the infiltration group, the wounds were infiltrated with 0.5% ropivacaine by the surgeon with a placebo paravertebral block. Subsequently, patient-controlled intravenous morphine analgesia and paracoxib were administered. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were visual analog scale (VAS) pain scores at rest and on cough 0, 2, 6, and 24 hours after surgery. The secondary endpoints were the total morphine during postoperative 0 hours to 24 hours, adverse events, and patient satisfaction with the analgesia. Sixty-one patients completed the study. VAS score on cough at each time point was significantly lower (p<0.05) and median (25th, 75th) morphine consumption was lower in the PVB group than in the infiltration group (26 [10, 35] mg and 42 [29, 58] mg, p<0.001, respectively). There was no difference in VAS score at rest. Patients in the PVB group had higher satisfaction with analgesia than in the infiltration group (p = 0.003). CONCLUSIONS: As part of the multimodal postoperative analgesia, intraoperative paravertebral block provided better dynamic pain relief and reduced morphine consumption compared with local wound infiltration.


Assuntos
Analgesia/métodos , Bloqueio Nervoso/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/terapia , Cirurgia Torácica Vídeoassistida/métodos , Cicatrização/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Terapia Combinada/métodos , Método Duplo-Cego , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Estudos Prospectivos , Vértebras Torácicas
14.
J Gen Virol ; 95(Pt 3): 671-678, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24385436

RESUMO

Bovine herpesvirus type 5 (BoHV-5) and bovine herpesvirus 1 (BoHV-1) are two closely related viruses. However, BoHV-5 is responsible for fatal meningitis in calves, while BoHV-1 is associated with infectious rhinotracheitis in cattle, and the mechanism by which the two viruses cause different symptoms is not well understood. In this study, we identified 11 microRNA (miRNA) genes, encoded by the BoHV-5 genome, that were processed into 16 detectable mature miRNAs in productive infection as determined by deep sequencing. We found that 6 out of 16 miRNA genes were present as two copies in the internal repeat and terminal repeat regions, resulting in a total of 17 miRNA-encoding loci distributed in both DNA strands. Surprisingly, BoHV-5 shared only one conservative miRNA with BoHV-1, which was located upstream of the origin of replication. Furthermore, in contrast to BoHV-1, no miRNAs were detected in the unique short region and locus within or near the bovine infected-cell protein 0 and latency-related genes. Variations in both the 5' and 3' ends of the reference sequence were observed, resulting in more than one isoform for each miRNA. All of the 16 miRNAs were detectable by stem-loop reverse transcriptase-PCR. The miRNAs with high read numbers were subjected to Northern blot analysis, and all pre-miRNAs and one mature miRNA were detected. Collectively, the data suggest that BoHV-5 encodes a different pattern of miRNAs, which may regulate the life cycle of BoHV-5 and might account for the different pathogenesis of this virus compared with BoHV-1.


Assuntos
Doenças dos Bovinos/virologia , Infecções por Herpesviridae/veterinária , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 5/genética , MicroRNAs/genética , RNA Viral/genética , Animais , Sequência de Bases , Bovinos , Infecções por Herpesviridae/virologia , Herpesvirus Bovino 1/metabolismo , Herpesvirus Bovino 5/metabolismo , MicroRNAs/metabolismo , Dados de Sequência Molecular , RNA Viral/metabolismo
15.
Sci Rep ; 14(1): 4125, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374336

RESUMO

Primary effusion lymphoma (PEL) and a form of multicentric Castleman's disease (MCD) are both caused by Kaposi sarcoma herpesvirus (KSHV). There is a critical need for improved therapies for these disorders. The IL-6/JAK/STAT3 pathway plays an important role in the pathogenesis of both PEL and KSHV-MCD. We explored the potential of JAK inhibitors for use in PEL and KSHV-MCD, and found that pacritinib was superior to others in inhibiting the growth of PEL cell lines. Pacritinib induced apoptosis in PEL cells and inhibited STAT3 and NF-κB activity as evidenced by reduced amount of phosphorylated moieties. Pacritinib also inhibits FLT3, IRAK1, and ROS1; studies utilizing other inhibitors of these targets revealed that only FLT3 inhibitors exhibited similar cell growth inhibitory effects. FLT3's likely contribution to pacritinib's cell growth inhibition was further demonstrated by siRNA knockdown of FLT3. RNA sequencing and RT-PCR showed that many key host genes including cyclins and IL-6 were downregulated by pacritinib, while KSHV genes were variably altered. Finally, pacritinib suppressed KSHV viral IL-6-induced human IL-6 and IL-10 production in peripheral blood mononuclear cells, which may model an important step in KSHV-MCD pathogenesis. These results suggest that pacritinib warrants testing for the treatment of KSHV-MCD and PEL.


Assuntos
Hidrocarbonetos Aromáticos com Pontes , Hiperplasia do Linfonodo Gigante , Herpesvirus Humano 8 , Linfoma de Efusão Primária , Pirimidinas , Humanos , Interleucina-6/metabolismo , Linfoma de Efusão Primária/metabolismo , Citocinas/metabolismo , Leucócitos Mononucleares/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Virais/genética , Herpesvirus Humano 8/genética , Proliferação de Células
16.
Eur J Med Chem ; 275: 116539, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38878515

RESUMO

AML is an aggressive malignancy of immature myeloid progenitor cells. Discovering effective treatments for AML through cell differentiation and anti-proliferation remains a significant challenge. Building on previous studies on CDK2 PROTACs with differentiation-inducing properties, this research aims to enhance CDKs degradation through structural optimization to facilitate the differentiation and inhibit the proliferation of AML cells. Compound C3, featuring a 4-methylpiperidine ring linker, effectively degraded CDK2 with a DC50 value of 18.73 ± 10.78 nM, and stimulated 72.77 ± 3.51 % cell differentiation at 6.25 nM in HL-60 cells. Moreover, C3 exhibited potent anti-proliferative activity against various AML cell types. Degradation selectivity analysis indicated that C3 could be endowed with efficient degradation of CDK2/4/6/9 and FLT3, especially FLT3-ITD in MV4-11 cells. These findings propose that C3 combined targeting CDK2/4/6/9 and FLT3 with enhanced differentiation and proliferation inhibition, which holds promise as a potential treatment for AML.

17.
J Phys Chem A ; 117(17): 3599-607, 2013 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-23548038

RESUMO

In this article, we discuss a study of the influence of Nd(3+) and Yb(3+) dopants on the spectroscopic behavior of Y2O3 ceramic polycrystals, by using Raman and cathodoluminescence (CL) spectroscopy. Doping with Yb at 1 at % results in a blue shift of the Raman band but has no pronounced influence on the intrinsic emission of Y2O3, while doping with Nd shows a red shift of the Raman band and markedly enhances the oxygen vacancy related 380 nm CL band. Lattice distortion induced by the alien ion incorporation and variations of effective absorption coefficients by adding different dopants were assessed using Raman spectroscopy. Moreover, both CL and Raman spectroscopies were applied to examine the homogeneity and distribution of the dopants throughout the ceramic microstructure. Visualization of sample homogeneity was made available by hyperspectral imaging of the local intensity of CL bands, while spectral deconvolution was performed to retrieve local structural variations at grain boundaries. We also confirmed that the combination of Raman and CL spectroscopies leads to a reliable and useful methodology for the examination of dopants in yttria ceramic materials.


Assuntos
Cerâmica/química , Medições Luminescentes , Neodímio/química , Itérbio/química , Ítrio/química , Tamanho da Partícula , Análise Espectral Raman , Propriedades de Superfície
18.
Anesth Analg ; 116(4): 804-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23460566

RESUMO

BACKGROUND: While lipid emulsion may reverse the systemic toxicity of bupivacaine, the pharmacokinetics and tissue distribution of bupivacaine after lipid emulsion infusion are not clear. In this study, we assessed the influence of lipid emulsion administration on the pharmacokinetics and tissue distribution of bupivacaine. METHODS: Rats in the lipid group were administered IV bupivacaine at the rate of 2 mg·kg(-1)·min(-1) for 4 minutes, and then were treated with an infusion of 30% lipid emulsion at the rate of 3 mL·kg(-1)·min(-1) for 5 minutes; saline was substituted in the control group (n = 6 for pharmacokinetics). We then randomly assigned 100 rats into the lipid group and control group (n = 50 for distribution). The toxicity model and treatment were the same as the pharmacokinetic portion. Plasma and tissues including brain, heart, liver, spleen, lung, kidney, omentum, and muscle were collected. The plasma concentration and tissue content of bupivacaine were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the pharmacokinetics of bupivacaine. RESULTS: All data are shown as mean ± SD. After treatment with the lipid emulsion, t1/2ß of bupivacaine in the lipid group was significantly shorter (110 ± 25 minutes vs 199 ± 38 minutes, P = 0.001), the clearance was higher (14 ± 4 mL·mg(-1)·kg(-1) vs 9 ± 4 mL·mg(-1)·kg(-1), P = 0.038), and the t1/2α was longer than that of the control group (4 ± 1 minutes vs 2 ± 1 minutes, P = 0.014); the K12 in the lipid group was less than that of the control group (0.13 ± 0.04 vs 0.32 ± 0.13, P = 0.011). In the lipid group, the bupivacaine content in heart, brain, lung, kidney, and spleen was lower than that in the control group, but higher in the liver at 20, 30, and 45 minutes. CONCLUSION: The lipid sink phenomenon was observed in this study. The use of a lipid emulsion accelerated the elimination of bupivacaine.


Assuntos
Anestésicos Locais/farmacocinética , Bupivacaína/farmacocinética , Emulsões Gordurosas Intravenosas/farmacologia , Animais , Área Sob a Curva , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Modelos Estatísticos , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Distribuição Tecidual
19.
Anesth Analg ; 117(2): 507-13, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23744953

RESUMO

BACKGROUND: The transversus abdominis plane (TAP) block has been shown to provide effective postoperative analgesia in lower abdominal surgery. Subcostal TAP block has also been proposed as a new technique to provide analgesia for the supraumbilical abdomen. We compared the analgesic and opioid-sparing effects of a single-injection subcostal TAP block with continuous thoracic epidural analgesia and IV opioid analgesia. METHODS: Ninety patients undergoing elective radical gastrectomy were randomized to receive either combined general-subcostal TAP anesthesia (group TAP), combined general-epidural anesthesia (group EA), or general anesthesia (group GA), and were analyzed on an intention-to-treat basis. In group TAP, a bilateral subcostal TAP block was performed after induction of general anesthesia using 20 mL of 0.375% ropivacaine. In group EA, a thoracic epidural was placed between T8 and T9 and bolused with 8 mL of 0.25% ropivacaine before induction of general anesthesia. The epidural was maintained with 5 mL/h of 0.25% ropivacaine during the surgery. Group GA received standard general anesthesia. In the postanesthesia care unit (PACU), all groups received IV morphine titration for visual analog scale (VAS) pain scores >3. All patients were started on IV patient-controlled analgesia with morphine after morphine titration in the PACU, while group EA also had their epidural maintained with 5 mL/h of 0.125% bupivacaine with 8 µg/mL morphine. Patients were assessed in the PACU and at 1, 3, 6, 24, 48, and 72 hours postoperatively. Primary outcomes measured were morphine consumption at 24 hours and all VAS pain scores. RESULTS: Data from 82 of 90 (91.1%) patients were included in the study. Group TAP demonstrated decreased cumulative morphine consumption at 24 hours (98.75% confidence intervals, -29 to -9 mg) and noninferiority on VAS pain scores at all measurement times, as compared with group GA with standard opioid analgesia. However, group EA was superior to group TAP regarding cumulative morphine consumption at 24 hours (98.75% confidence intervals, -23 to -4 mg) and noninferior to group TAP on VAS pain scores at all comparison points. Group TAP had reduced morphine consumption from PACU admission to 6 hours as compared with group GA, but increased morphine consumption for 6 to 24 hours as compared with group EA. CONCLUSION: Single-injection subcostal TAP block was more effective than IV opioid analgesia, while continuous thoracic epidural analgesia was more effective than the single-injection subcostal TAP block.


Assuntos
Amidas/administração & dosagem , Analgesia Epidural/métodos , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Anestésicos Locais/administração & dosagem , Gastrectomia/efeitos adversos , Morfina/administração & dosagem , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Reto do Abdome/inervação , Administração Intravenosa , Idoso , Período de Recuperação da Anestesia , Anestesia Geral , Distribuição de Qui-Quadrado , China , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Valor Preditivo dos Testes , Sala de Recuperação , Ropivacaina , Fatores de Tempo , Resultado do Tratamento
20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 29(2): 332-6, 2012 Apr.
Artigo em Zh | MEDLINE | ID: mdl-22616185

RESUMO

Ultrasound images are easily corrupted by speckle noise, which limits its further application in medical diagnoses. An image de-noising method combining dual-tree complex wavelet transform (DT-CWT) with nonlinear diffusion is proposed in this paper. Firstly, an image is decomposed by DT-CWT. Then adaptive-contrast-factor diffusion and total variation diffusion are applied to high-frequency component and low-frequency component, respectively. Finally the image is synthesized. The experimental results are given. The comparisons of the image de-noising results are made with those of the image de-noising methods based on the combination of wavelet shrinkage with total variation diffusion, the combination of wavelet/multiwavelet with nonlinear diffusion. It is shown that the proposed image de-noising method based on DT-CWT and nonlinear diffusion can obtain superior results. It can both remove speckle noise and preserve the original edges and textural features more efficiently.


Assuntos
Artefatos , Interpretação de Imagem Assistida por Computador/métodos , Ultrassonografia/métodos , Análise de Ondaletas , Algoritmos , Humanos
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