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Superlattices-a periodic stacking of two-dimensional layers of two or more materials-provide a versatile scheme for engineering materials with tailored properties1,2. Here we report an intrinsic heterodimensional superlattice consisting of alternating layers of two-dimensional vanadium disulfide (VS2) and a one-dimensional vanadium sulfide (VS) chain array, deposited directly by chemical vapour deposition. This unique superlattice features an unconventional 1T stacking with a monoclinic unit cell of VS2/VS layers identified by scanning transmission electron microscopy. An unexpected Hall effect, persisting up to 380 kelvin, is observed when the magnetic field is in-plane, a condition under which the Hall effect usually vanishes. The observation of this effect is supported by theoretical calculations, and can be attributed to an unconventional anomalous Hall effect owing to an out-of-plane Berry curvature induced by an in-plane magnetic field, which is related to the one-dimensional VS chain. Our work expands the conventional understanding of superlattices and will stimulate the synthesis of more extraordinary superstructures.
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The scaling of silicon-based transistors at sub-ten-nanometre technology nodes faces challenges such as interface imperfection and gate current leakage for an ultrathin silicon channel1,2. For next-generation nanoelectronics, high-mobility two-dimensional (2D) layered semiconductors with an atomic thickness and dangling-bond-free surfaces are expected as channel materials to achieve smaller channel sizes, less interfacial scattering and more efficient gate-field penetration1,2. However, further progress towards 2D electronics is hindered by factors such as the lack of a high dielectric constant (κ) dielectric with an atomically flat and dangling-bond-free surface3,4. Here, we report a facile synthesis of a single-crystalline high-κ (κ of roughly 16.5) van der Waals layered dielectric Bi2SeO5. The centimetre-scale single crystal of Bi2SeO5 can be efficiently exfoliated to an atomically flat nanosheet as large as 250 × 200 µm2 and as thin as monolayer. With these Bi2SeO5 nanosheets as dielectric and encapsulation layers, 2D materials such as Bi2O2Se, MoS2 and graphene show improved electronic performances. For example, in 2D Bi2O2Se, the quantum Hall effect is observed and the carrier mobility reaches 470,000 cm2 V-1 s-1 at 1.8 K. Our finding expands the realm of dielectric and opens up a new possibility for lowering the gate voltage and power consumption in 2D electronics and integrated circuits.
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Grafite , Silício , Eletrônica , SemicondutoresRESUMO
Multiple myeloma (MM) remains incurable due to drug resistance. Ribosomal protein S3 (RPS3) has been identified as a non-Rel subunit of NF-κB. However, the detailed biological roles of RPS3 remain unclear. Here, we report for the first time that RPS3 is necessary for MM survival and drug resistance. RPS3 was highly expressed in MM, and knockout of RPS3 in MM inhibited cell growth and induced cell apoptosis both in vitro and in vivo. Overexpression of RPS3 mediated the proteasome inhibitor resistance of MM and shortened the survival of MM tumor-bearing animals. Moreover, our present study found an interaction between RPS3 and the thyroid hormone receptor interactor 13 (TRIP13), an oncogene related to MM tumorigenesis and drug resistance. We demonstrated that the phosphorylation of RPS3 was mediated by TRIP13 via PKCδ, which played an important role in activating the canonical NF-κB signaling and inducing cell survival and drug resistance in MM. Notably, the inhibition of NF-κB signaling by the small-molecule inhibitor targeting TRIP13, DCZ0415, was capable of triggering synergistic cytotoxicity when combined with bortezomib in drug-resistant MM. This study identifies RPS3 as a novel biomarker and therapeutic target in MM.
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Mieloma Múltiplo , NF-kappa B , Animais , NF-kappa B/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Inibidores de Proteassoma/farmacologia , Inibidores de Proteassoma/uso terapêutico , Proteínas Ribossômicas/genética , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Resistência a Medicamentos , Linhagem Celular TumoralRESUMO
It has been theoretically predicted that perturbation of the Berry curvature by electromagnetic fields gives rise to intrinsic nonlinear anomalous Hall effects that are independent of scattering. Two types of nonlinear anomalous Hall effects are expected. The electric nonlinear Hall effect has recently begun to receive attention, while very few studies are concerned with the magneto-nonlinear Hall effect. Here, we combine experiment and first-principles calculations to show that the kagome ferromagnet Fe_{3}Sn_{2} displays such a magneto-nonlinear Hall effect. By systematic field angular and temperature-dependent transport measurements, we unambiguously identify a large anomalous Hall current that is linear in both applied in-plane electric and magnetic fields, utilizing a unique in-plane configuration. We clarify its dominant orbital origin and connect it to the magneto-nonlinear Hall effect. The effect is governed by the intrinsic quantum geometric properties of Bloch electrons. Our results demonstrate the significance of the quantum geometry of electron wave functions from the orbital degree of freedom and open up a new direction in Hall transport effects.
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BACKGROUND: Pseudorabies virus (PRV) is one of the major viral pathogens leading to reproductive disorders in swine. However, little is known about the effects of PRV infection on porcine reproductive system. Ovarian granulosa cells are somatic cells surrounding oocytes in ovary and required for folliculogenesis. The present study aimed to investigate the interference of PRV on functions of porcine ovarian granulosa cells in vitro. METHODS: Primary granulosa cells were isolated from porcine ovaries. To investigate the PRV infectivity, transmission electron microscopy (TEM) was used to check the presence of viral particles, and the expression of viral gE gene was detected by quantitative real-time PCR (qPCR) in PRV-inoculated cells. After PRV infection, cell viability was detected by MTS assay, Ki67 for proliferative status was determined by immunofluorescence assay (IFA), cell cycle and apoptosis were detected by flow cytometry, and progesterone (P4) and estradiol (E2) were determined by radioimmunoassay. The checkpoint genes of cell cycle and apoptosis-related proteins were studied by qPCR and western blotting. RESULTS: Virus particles were observed in the nucleus and cytoplasm of PRV-infected granulosa cells by TEM imaging, and the expression of viral gE gene increased in a time-dependent manner post infection. PRV infection inhibited cell viability and blocked cell cycle at S phase in porcine granulosa cells, accompanied by decreases in expression of Ki67 protein and checkpoint genes related to S phase. Radioimmunoassay revealed decreased levels in P4 and E2, and the expressions of key steroidogenic enzymes were also down-regulated post PRV-infection. In addition, PRV induced apoptosis with an increase in Bax expression and activation of caspase 9, and the phosphorylation of JNK, ERK and p38 MAPKs were significantly up-regulated in porcine ovarian granulosa cells post PRV infection. CONCLUSIONS: The data indicate that PRV causes infection on porcine ovarian granulosa cells and interferes the cell functions through apoptosis, and the MAPK signaling pathway is involved in the viral pathogenesis.
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Herpesvirus Suídeo 1 , Feminino , Suínos , Animais , Antígeno Ki-67 , Transdução de Sinais , Apoptose , Células da GranulosaRESUMO
BACKGROUND: Multiple myeloma (MM), an incurable disease owing to drug resistance, requires safe and effective therapies. Norcantharidin (NCTD), an active ingredient in traditional Chinese medicines, possesses activity against different cancers. However, its toxicity and narrow treatment window limit its clinical application. In this study, we synthesized a series of derivatives of NCTD to address this. Among these compounds, DCZ5417 demonstrated the greatest anti-MM effect and fewest side effects. Its anti-myeloma effects and the mechanism were further tested. METHODS: Molecular docking, pull-down, surface plasmon resonance-binding, cellular thermal shift, and ATPase assays were used to study the targets of DCZ5417. Bioinformatic, genetic, and pharmacological approaches were used to elucidate the mechanisms associated with DCZ5417 activity. RESULTS: We confirmed a highly potent interaction between DCZ5417 and TRIP13. DCZ5417 inhibited the ATPase activity of TRIP13, and its anti-MM activity was found to depend on TRIP13. A mechanistic study verified that DCZ5417 suppressed cell proliferation by targeting TRIP13, disturbing the TRIP13/YWHAE complex and inhibiting the ERK/MAPK signaling axis. DCZ5417 also showed a combined lethal effect with traditional anti-MM drugs. Furthermore, the tumor growth-inhibitory effect of DCZ5417 was demonstrated using in vivo tumor xenograft models. CONCLUSIONS: DCZ5417 suppresses MM progression in vitro, in vivo, and in primary cells from drug-resistant patients, affecting cell proliferation by targeting TRIP13, destroying the TRIP13/YWHAE complex, and inhibiting ERK/MAPK signaling. These results imply a new and effective therapeutic strategy for MM treatment.
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Mieloma Múltiplo , Humanos , Proteínas 14-3-3/metabolismo , Apoptose , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Simulação de Acoplamento Molecular , Mieloma Múltiplo/metabolismo , Transdução de Sinais , AnimaisRESUMO
Adaptive optics systems for large-aperture solar telescopes, especially multiconjugate adaptive optics systems, suffer from a fundamental trade-off between wavefront sampling rate and sub-aperture resolution. We introduce an enhanced-resolution Shack-Hartmann wavefront sensing method that decouples sub-aperture resolution from the desired wavefront sampling rate. We experimentally verified the validity of this method. Results show that by synthesizing multiple low-spatial samplings, this method is capable to sense higher-frequency aberrations beyond any low-spatial sampling involved in the synthesis, and it allows higher sub-aperture resolution and higher operating bandwidths, which can better fulfill the needs of solar adaptive optics.
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Despite significant improvement in the prognosis of multiple myeloma (MM), the disease remains incurable; thus, more effective therapies are required. Ribonucleoside-diphosphate reductase subunit M2 (RRM2) is significantly associated with drug resistance, rapid relapse, and poor prognosis. Previously, we found that 4-hydroxysalicylanilide (osalmid), a specific inhibitor of RRM2, exhibits anti-MM activity in vitro, in vivo, and in human patients; however, the mechanism remains unclear. Osalmid inhibits the translocation of RRM2 to the nucleus and stimulates autophagosome synthesis but inhibits subsequent autophagosome-lysosome fusion. We confirm that RRM2 binds to receptor-interacting protein kinase 3 (RIPK3) and reduces RIPK3, inhibiting autophagosome-lysosome fusion. Interestingly, the combination of osalmid and bafilomycin A1 (an autophagy inhibitor) depletes RIPK3 and aggravates p62 and autophagosome accumulation, leading to autophagic cell death. Combination therapy demonstrates synergistic cytotoxicity both in vitro and in vivo. Therefore, we propose that combining osalmid and bafilomycin A1(BafA1) may have clinical benefits against MM.
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Multiple myeloma (MM), the second most common haematological malignancy, is currently incurable because patients often develop multiple drug resistance and experience subsequent relapse of the disease. This study aims to identify a potential therapeutic agent that can counter bortezomib (BTZ) resistance in MM. DCZ0358, a novel alkaloid compound, is found to exert potent cytotoxic effects against BTZ-resistant MM cells in vivo and in vitro. The anti-myeloma activity of DCZ0358 is associated with inhibition of cell proliferation, promotion of cell apoptosis via caspase-mediated apoptotic pathways, and induction of G0/G1 phase arrest via downregulation of cyclin D1, CDK4, and CDK6. Further investigation of the molecular mechanism shows that DCZ0358 suppresses the JAK2/STAT3 signaling pathway. In conclusion, DCZ0358 can successfully counter BTZ resistance in MM cells. This study provides evidence that warrants future preclinical assessments of DCZ0358 as a therapeutic agent against BTZ resistance in MM.
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Alcaloides , Antineoplásicos , Mieloma Múltiplo , Humanos , Bortezomib/farmacologia , Bortezomib/metabolismo , Bortezomib/uso terapêutico , Mieloma Múltiplo/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Alcaloides/farmacologia , Linhagem Celular Tumoral , Apoptose , Proliferação de Células , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
Multiple myeloma (MM) is characterized by excessive aggregation of B-cell-derived malignant plasma cells in the hematopoietic system of bone marrow. Previously, we synthesized an innovative molecule named dihydrocelastrol (DHCE) from celastrol, a triterpene purified from medicinal plant Tripterygium wilfordii. Herein, we explore the therapeutic properties and latent signal transduction mechanism of DHCE action in bortezomib (BTZ)-resistant (BTZ-R) MM cells. In this study, we first report that DHCE shows antitumor activities in vitro and in vivo and exerts stronger inhibitory effects than celastrol on BTZ-R cells. We find that DHCE inhibits BTZ-R cell viability by promoting apoptosis via extrinsic and intrinsic pathways and suppresses BTZ-R MM cell proliferation by inducing G0/G1 phase cell cycle arrest. In addition, inactivation of JAK2/STAT3 and PI3K/Akt pathways are involved in the DHCE-mediated antitumor effect. Simultaneously, DHCE acts synergistically with BTZ on BTZ-R cells. PSMB5, a molecular target of BTZ, is overexpressed in BTZ-R MM cells compared with BTZ-S MM cells and is demonstrated to be a target of STAT3. Moreover, DHCE downregulates PSMB5 overexpression in BTZ-R MM cells, which illustrates that DHCE overcomes BTZ resistance through increasing the sensitivity of BTZ in resistant MM via inhibiting STAT3-dependent PSMB5 regulation. Overall, our findings imply that DHCE may become a potential therapeutic option that warrants clinical evaluation for BTZ-R MM.
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Antineoplásicos , Mieloma Múltiplo , Humanos , Bortezomib/farmacologia , Bortezomib/metabolismo , Bortezomib/uso terapêutico , Mieloma Múltiplo/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Apoptose , Proliferação de Células , Complexo de Endopeptidases do Proteassoma/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismoRESUMO
Tilting the Weyl cone breaks the Lorentz invariance and enriches the Weyl physics. Here, we report the observation of a magnetic-field-antisymmetric Seebeck effect in a tilted Weyl semimetal, Co_{3}Sn_{2}S_{2}. Moreover, it is found that the Seebeck effect and the Nernst effect are antisymmetric in both the in-plane magnetic field and the magnetization. We attribute these exotic effects to the one-dimensional chiral anomaly and phase space correction due to the Berry curvature. The observation is further reproduced by a theoretical calculation, taking into account the orbital magnetization.
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BACKGROUND: Aberrant DNA repair pathways contribute to malignant transformation or disease progression and the acquisition of drug resistance in multiple myeloma (MM); therefore, these pathways could be therapeutically exploited. Ribonucleotide reductase (RNR) is the rate-limiting enzyme for the biosynthesis of deoxyribonucleotides (dNTPs), which are essential for DNA replication and DNA damage repair. In this study, we explored the efficacy of the novel RNR inhibitor, 4-hydroxysalicylanilide (HDS), in myeloma cells and xenograft model. In addition, we assessed the clinical activity and safety of HDS in patients with MM. METHODS: We applied bioinformatic, genetic, and pharmacological approaches to demonstrate that HDS was an RNR inhibitor that directly bound to RNR subunit M2 (RRM2). The activity of HDS alone or in synergy with standard treatments was evaluated in vitro and in vivo. We also initiated a phase I clinical trial of single-agent HDS in MM patients (ClinicalTrials.gov: NCT03670173) to assess safety and efficacy. RESULTS: HDS inhibited the activity of RNR by directly targeting RRM2. HDS decreased the RNR-mediated dNTP synthesis and concomitantly inhibited DNA damage repair, resulting in the accumulation of endogenous unrepaired DNA double-strand breaks (DSBs), thus inhibiting MM cell proliferation and inducing apoptosis. Moreover, HDS overcame the protective effects of IL-6, IGF-1 and bone marrow stromal cells (BMSCs) on MM cells. HDS prolonged survival in a MM xenograft model and induced synergistic anti-myeloma activity in combination with melphalan and bortezomib. HDS also showed a favorable safety profile and demonstrated clinical activity against MM. CONCLUSIONS: Our study provides a rationale for the clinical evaluation of HDS as an anti-myeloma agent, either alone or in combination with standard treatments for MM. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03670173, Registered 12 September 2018.
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Mieloma Múltiplo , Ribonucleotídeo Redutases , Quebras de DNA de Cadeia Dupla , Dano ao DNA , Reparo do DNA , Replicação do DNA , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Ribonucleotídeo Redutases/genética , Ribonucleotídeo Redutases/metabolismoRESUMO
Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 µm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 µmol·L -1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L -1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.
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Técnicas Analíticas Microfluídicas , Microfluídica , Movimento Celular , Quimiotaxia , Desenho de Equipamento , Dispositivos Lab-On-A-Chip , Neutrófilos , Reprodutibilidade dos TestesRESUMO
Weyl semimetals host a variety of exotic effects that have no counterpart in conventional materials, such as the chiral anomaly and magnetic monopole in momentum space. These effects give rise to unusual transport properties, including a negative magnetoresistance and a planar Hall effect, etc. Here, we report a new type of Hall and magnetoresistance effect in a magnetic Weyl semimetal. Unlike antisymmetric (with respect to either magnetic field or magnetization) Hall and symmetric magnetoresistance in conventional materials, the discovered magnetoresistance and Hall effect are antisymmetric in both magnetic field and magnetization. We show that the Berry curvature, the tilt of the Weyl node, and the chiral anomaly synergically produce these phenomena. Our results reveal a unique property of Weyl semimetals with broken time reversal symmetry.
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Mobile sensing based on the integration of microfluidic devices and smartphones, so-called MS2 technology, has enabled many applications over recent years and continues to stimulate growing interest in both research communities and industries. In particular, MS2 technology has been proven to be able to be applied to molecular diagnostic analysis and can be implemented for basic research and clinical testing. However, the currently reported MS2-based nucleic acid analysis system has limited use in practical applications, because it is not integrated with quantitative PCR, multiplex PCR, and isothermal amplification functions, and lacks temperature control, image acquisition and real-time processing units with excellent performance. To provide a more universal and powerful platform, we here developed a novel MS2 device by integrating a thermocycler, a multi fluorescence detection unit, a PCR chip, an isothermal chip, and a smartphone. The MS2 device was approximately 325 mm (L) × 200 mm (W) × 200 mm (H) in volume and only 5 kg in weight, and showed an average power consumption of about 38.4 W. The entire nucleic acid amplification and analysis could be controlled through a self-made smartphone App. The maximum heating and cooling rates were 5 °C s-1 and 4 °C s-1, respectively. The entire PCR could be completed within 65 min. The temperature uniformity was less than 0.1 °C. Besides, the temperature stability over time (30 min) was within ±0.04 °C. Four optical channels were integrated (FAM, HEX, TAMRA, and ROX) on the MS2 device. In particular, the PCR-based detection sensitivity reached 1 copy per µL, and the amplification efficiency was calculated to be 106.8%. Besides, the MS2 device also was compatible with multiplex PCR and isothermal amplification. In short, the MS2 device showed performance consistent with that of traditional commercial equipment. Thus, the MS2 device provides an easy and integrated experimental platform for molecular diagnostic-related research and potential medical diagnostic applications.
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Técnicas Analíticas Microfluídicas , Ácidos Nucleicos , Dispositivos Lab-On-A-Chip , Técnicas de Amplificação de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , SmartphoneRESUMO
Resveratrol, a natural compound extracted from the skins of grapes, berries, or other fruits, has been shown to have anti-tumor effects against multiple myeloma (MM) via promoting apoptosis and inhibiting cell viability. In addition to apoptosis, autophagy also plays a significant role in anti-tumor effects. However, whether autophagy is involved in anti-MM activity of resveratrol remains unclear. In this study, human MM cell lines U266, RPMI-8226, and NCI-H929 were treated with resveratrol. Cell Counting Kit-8 assay and colony formation assay were used to measure cell viability. Western blot analysis was used to detect apoptosis- and autophagy-associated proteins. 3-Methyladenine (3-MA) was applied to inhibit autophagy. Results showed that resveratrol inhibited cell viability and colony formation via promoting apoptosis and autophagy in MM cell lines U266, RPMI-8226, and NCI-H929. Resveratrol promoted apoptosis-related proteins, Caspase-3 activating poly-ADP-ribose polymerase and Caspase-3 cleavage, and decreased the protein level of Survivin in a dose-dependent manner. Additionally, resveratrol upregulated the levels of LC3 and Beclin1 in a dose-dependent way, indicating that autophagy might be implicated in anti-MM effect of resveratrol. Furthermore, 3-MA relieved the cytotoxicity of resveratrol by blocking the autophagic flux. Resveratrol increased the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream substrates p70S6K and 4EBP1 in a dose-dependent manner, leading to autophagy. Therefore, our results suggest that resveratrol exerts anti-MM effects through apoptosis and autophagy, which can be used as a new therapeutic strategy for MM in clinic.
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Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Mieloma Múltiplo/metabolismo , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Monofosfato de Adenosina/metabolismo , Proteína Beclina-1/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Mieloma Múltiplo/patologia , Fosforilação/efeitos dos fármacosRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, characterized by high heterogeneity. The poor outcome of a portion of patients who suffer relapsing or resistant to conventional treatment impels the development of novel agents for DLBCL. DCZ0825 is a novel compound derived from pterostilbene and osalmide, whose antitumor activities have drawn our attention. In this study, we found that DCZ0825 exhibited high cytotoxicity toward DLBCL cell lines in a dose- and time-dependent manner, as revealed by cell counting kit-8 assay. Flow cytometry and western blot analysis results showed that DCZ0825 also promoted cell apoptosis via both extrinsic and intrinsic apoptosis pathways mediated by caspase. In addition, DCZ0825 induced cell cycle arrest in the G2/M phase by downregulating Cdc25C, CDK1, and Cyclin B1, thus interfering with cell proliferation. Further investigation showed the involvement of the phosphatidylinositol 3-kinase (PI3K)âAKTâmTOR/JNK pathway in the efficacy of DCZ0825 against DLBCL. Remarkably, DCZ0825 also exerted notable cytotoxic effects in vivo as well, with low toxicity to important internal organs such as the liver and kidney. Our results suggest that DCZ0825 may have the potential to become a novel anti-DLBCL agent or to replenish the conventional therapeutic scheme of DLBCL.
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Antineoplásicos/farmacologia , Linfoma Difuso de Grandes Células B , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologiaRESUMO
One of the characteristics of topological materials is their nontrivial Berry phase. Experimental determination of this phase largely relies on a phase analysis of quantum oscillations. We study the angular dependence of the oscillations in a Dirac material [Formula: see text] and observe a striking spin-zero effect (i.e., vanishing oscillations accompanied with a phase inversion). This indicates that the Berry phase in [Formula: see text] remains nontrivial for arbitrary field direction, in contrast with previous reports. The Zeeman splitting is found to be proportional to the magnetic field based on the condition for the spin-zero effect in a Dirac band. Moreover, it is suggested that the Dirac band in [Formula: see text] is likely transformed into a line node other than Weyl points for the field directions at which the spin zero occurs. The results underline a largely overlooked spin factor when determining the Berry phase from quantum oscillations.
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OBEJECTIVE: To develop a method for the determination of 13 antibiotics in 8 classes for desinfection products by ulta-high perfomance chromatography-tandem mass spectrometry(UPLC-MS/MS). METHODS: Samples were extracted by methanol or acetonitrile. The target compouds were separated on a Waters HSS T3 column(100 mm×2. 1 mm, 1. 8 µm), and detected by triple quadrupole tandem mass spectrometer. RESULTS: The 13 selected antibiotics showed good linear relationships in the range of 4-100 µg/L and the correlation coefficients(r~2) were all above 0. 991. The limits of detection ranged from 2 to 25 µg/kg. The recovery rates at three spiked levels(low, medium and high) in three dosage forms of disinfection products were in the range of 71. 2%-130. 4%, and the relative standard deviations(RSD) were all less than 11. 3%, which could meet the detection requirements of illegal addition of antibiotics in disinfection products. Ofloxacin at a concentration of 21. 1 mg/kg was found in a cream disinfection product by the developed method, and no related drugs were detected in other samples. CONCLUSION: This method is simple, reliable, reproducible, which covers a wide range of antibiotics, and provides technical support for monitoring the illegal addition of antibiotics in disinfection products.