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1.
Sci Adv ; 10(16): eadn4524, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38630830

RESUMO

Bio-inspired transistor synapses use solid electrolytes to achieve low-power operation and rich synaptic behaviors via ion diffusion and trapping. While these neuromorphic devices hold great promise, they still suffer from challenges such as high leakage currents and power consumption, electrolysis risk, and irreversible conductance changes due to long-range ion migrations and permanent ion trapping. In addition, their response to light is generally limited because of "exciton-polaron quenching", which restricts their potential in in-sensor neuromorphic visions. To address these issues, we propose replacing solid electrolytes with polyzwitterions, where the cation and anion are covalently concatenated via a flexible alkyl chain, thus preventing long-range ion migrations while inducing good photoresponses to the transistors via interfacial charge trapping. Our detailed studies reveal that polyzwitterion-based transistors exhibit optoelectronic synaptic behavior with ultralow-power consumption (~250 aJ per spike) and enable high-performance in-sensor reservoir computing, achieving 95.56% accuracy in perceiving the trajectory of moving basketballs.

2.
Phys Rev Lett ; 132(10): 106601, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38518320

RESUMO

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.

3.
Adv Mater ; : e2401294, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38547590

RESUMO

Conventional security inks, generally directly printed on the data page surface, are vulnerable to counterfeiters, thereby raising the risk of chemical structural deciphering. In fact, polymer film-based data pages with customized patterns embedded within polymer matrix, rather than printed on the surface, emerge as a promising solution. Therefore, the key lies in developing fluorophores offering light dose-controlled fluorescent color inside polymer matrices. Though conventional fluorophores often suffer from photobleaching and uncontrolled photoreactions, disqualifying them for this purpose. Herein a diphenanthridinylfumaronitrile-based phototransformers (trans-D5) that undergoes photoisomerization and subsequent photocyclization during photopolymerization of the precursor, successively producing cis- and cyclo-D5 with stepwise redshifted solid-state emissions is developed. The resulting cyclo-D5 exhibits up to 172 nm emission redshift in rigidifying polymer matrices, while trans-D5 experiences a slightly blueshifted emission (≈28 nm), cis-D5 undergoes a modest redshift (≈14 nm). The markedly different rigidochromic behaviors of three D5 molecules within polymer matrices enable multicolor photochemical printing with a broad hue ranging from 38 to 10 via an anticlockwise direction in Munsell color space, yielding indecipherable fluorescent patterns in polymer films. This work provides a new method for document protection and implements advanced security features that are unattainable with conventional inks.

4.
Virol J ; 21(1): 25, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263223

RESUMO

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.


Assuntos
Herpesvirus Suídeo 1 , Feminino , Suínos , Animais , Antígeno Ki-67 , Transdução de Sinais , Apoptose , Células da Granulosa
5.
Int Immunopharmacol ; 127: 111446, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38157697

RESUMO

Multiple myeloma (MM) is an incurable and recurrent malignancy characterized by abnormal plasma cell proliferation. There is an urgent need to develop effective drugs in MM. DCZ0825 is a small molecule compound derived from pterostilbene with direct anti-myeloma activity and indirect immune-killing effects though reversal of the immunosuppression. DCZ0825 inhibits the activity and proliferation of MM cells causing no significant toxicity to normal cells. Using flow cytometry, this study found that DCZ0825 induced caspase-dependent apoptosis in MM cells and arrested the cell cycle in the G2/M phase by down-regulating CyclinB1, CDK1 and CDC25. Moreover, DCZ0825 up-regulated IRF3 and IRF7 to increase IFN-γ, promoting M2 macrophages to transform into M1 macrophages, releasing the immunosuppression of CD4T cells and stimulated M1 macrophages and Th1 cells to secrete more INF-γ to form immune killing effect on MM cells. Treatment with DCZ0825 resulted in an increased proportion of positive regulatory cells such as CD4T, memory T cells, CD8T, and NK cells, with downregulation of the proportion of negative regulatory cells such as Treg cells and MDSCs. In conclusion, DCZ0825 is a novel compound with both antitumor and immunomodulatory activity.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Recidiva Local de Neoplasia , Macrófagos , Células Th1 , Imunomodulação
6.
Opt Lett ; 48(21): 5691-5694, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910735

RESUMO

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.

7.
Int Immunopharmacol ; 125(Pt A): 111139, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913572

RESUMO

The most common neoplasm among adult lymphomas is diffuse large B-cell lymphoma (DLBCL), typically characterized by pain-free and progressive lymph node enlargement. Due to high heterogeneity of DLBCL, 30-40 % of patients are resistant to R-CHOP standard chemoimmunotherapy. DCZ0358 is a new compound designed and synthesized from berberine by our group and the molecular mechanism by which it inhibited DLBCL growth has attracted our widespread attention. In this study, we employed the CCK8 assay to reveal that DCZ0358 inhibited proliferation in a dependent manner of time and dosage of DLBCL cells. Moreover, flowcytometry and western blot results showed that DCZ0358 downregulated the expression of CDK4, CDK6 and CyclinD1 to block cell cycle progression in G0/G1 phase. Furthermore, DCZ0358 enhanced mitochondrial membrane potential depolarization, promoted mitochondrial permeability transport pore openness, increased cytoplastic Ca2+ levels and decreased intracellular adenosine triphosphate production, which led to mitochondrial dysfunction. In particular, DCZ0358 treatment triggered cell apoptosis and elevated intracellular reactive oxygen species (ROS) levels, which subsequently mediated JNK pathway activation. Further research indicated the pre-treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358. Most importantly, DCZ0358 exhibited synergistic anti-tumor effects when combined with etoposide, a common clinical anti-DLBCL drug, both in vitro and certainly in vivo. Above results demonstrated anti-tumor molecular mechanism of DCZ0358 in DLBCL cells and highlighted the ROS/JNK/DNA damage pathway as a potential target in therapies, which have implications for the development of more effective clinical treatments for DLBCL.


Assuntos
Berberina , Linfoma Difuso de Grandes Células B , Humanos , Apoptose , Berberina/farmacologia , Linhagem Celular Tumoral , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Sistema de Sinalização das MAP Quinases , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
8.
Cancer Med ; 12(23): 21321-21334, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37942576

RESUMO

BACKGROUND: Thyroid hormone receptor interacting protein 13 (Trip13) is an AAA-ATPase that regulates the assembly or disassembly protein complexes and mediates Double-strand breaks (DSBs) repair. Overexpression of Trip13 has been detected in many cancers and is associated with myeloma progression, disease relapse and poor prognosis inmultiple myeloma (MM). METHODS: We have identified a small molecular, TI17, through a parallel compound-centric approach, which specifically targets Trip13. To identify whether TI17 targeted Trip13, pull-down and nuclear magnetic resonance spectroscopy (NMR) assays were performed. Cell counting kit-8, clone formation, apoptosis and cell cycle assays were applied to investigate the effects of TI17. We also utilized a mouse model to investigate the effects of TI17 in vivo. RESULTS: TI17 effectively inhibited the proliferation of MM cells, and induced the cycle arrest and apoptosis of MM cells. Furthermore, treatment with TI17 abrogates tumor growth and has no apparent side effects in mouse xenograft models. TI17 specifically impaired Trip13 function of DSBs repair and enhanced DNA damage responses in MM. Combining with melphalan or HDAC inhibitor panobinostat triggers synergistic anti-MM effect. CONCLUSIONS: Our study suggests that TI17 could be acted as a specific inhibitor of Trip13 and supports a preclinical proof of concept for therapeutic targeting of Trip13 in MM.


Assuntos
Mieloma Múltiplo , Humanos , Animais , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Quebras de DNA de Cadeia Dupla , Recidiva Local de Neoplasia , Proteínas de Ciclo Celular/metabolismo , Reparo do DNA , Ciclo Celular
9.
Acta Biochim Biophys Sin (Shanghai) ; 55(12): 1884-1891, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38009004

RESUMO

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.


Assuntos
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/metabolismo
10.
J Transl Med ; 21(1): 858, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012658

RESUMO

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.


Assuntos
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 , Animais
11.
Adv Mater ; 35(49): e2306260, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37660306

RESUMO

The dielectric layer is crucial in regulating the overall performance of field-effect transistors (FETs), the key component in central processing units, sensors, and displays. Despite considerable efforts being devoted to developing high-permittivity (k) dielectrics, limited progress is made due to the inherent trade-off between dielectric constant and loss. Here, a solution is presented by designing a monodispersed disk-shaped Ce-Al-O-macrocycle as a dopant in polymer dielectrics. The molecule features a central Ce(III) core connected with eight Al atoms through sixteen bridging hydroxyls and eight 3-aminophenyl peripheries. The incorporation of this macrocycle in polymer dielectrics results in an up to sevenfold increase in dielectric constants and up to 89% reduction in dielectric loss at low frequencies. Moreover, the leakage-current densities decrease, and the breakdown strengths are improved by 63%. Relying on the above merits, FETs bearing cluster-doped polymer dielectrics give near three-orders source-drain current increments while maintaining low-level leakage/off currents, resulting in much higher charge-carrier mobilities (up to 2.45 cm2  V-1  s-1 ) and on/off ratios. This cluster-doping strategy is generalizable and shows great promise for ultralow-power photoelectric synapses and neuromorphic retinas. This work successfully breaks the trade-off between dielectric constant and loss and offers a unique design for polymer composite dielectrics.

12.
Haematologica ; 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37767568

RESUMO

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 delayed the survival of MM tumour-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 signalling and inducing cell survival and drug resistance in MM. Notably, the inhibition of NF-κB signalling 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.

13.
Arch Biochem Biophys ; 747: 109771, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37776936

RESUMO

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.

15.
Nat Mater ; 22(7): 832-837, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36894772

RESUMO

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.


Assuntos
Grafite , Silício , Eletrônica , Semicondutores
16.
Nat Commun ; 14(1): 835, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788224

RESUMO

Diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC) are the major histological types of gastric cancer (GC). The molecular mechanism underlying DGC and IGC differences are poorly understood. In this research, we carry out multilevel proteomic analyses, including proteome, phospho-proteome, and transcription factor (TF) activity profiles, of 196 cases covering DGC and IGC in Chinese patients. Integrative proteogenomic analysis reveals ARIDIA mutation associated with opposite prognostic effects between DGC and IGC, via diverse influences on their corresponding proteomes. Systematical comparison and consensus clustering analysis identify three subtypes of DGC and IGC, respectively, based on distinct patterns of the cell cycle, extracellular matrix organization, and immune response-related proteins expression. TF activity-based subtypes demonstrate that the disease progressions of DGC and IGC were regulated by SWI/SNF and NFKB complexes. Furthermore, inferred immune cell infiltration and immune clustering show Th1/Th2 ratio is an indicator for immunotherapeutic effectiveness, which is validated in an independent GC anti-PD1 therapeutic patient group. Our multilevel proteomic analyses enable a more comprehensive understanding of GC and can further advance the precision medicine.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Proteômica , Proteoma/genética , Mutação
17.
Acta Biochim Biophys Sin (Shanghai) ; 55(2): 215-224, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36815376

RESUMO

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.


Assuntos
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/metabolismo
18.
Nat Commun ; 14(1): 468, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709349

RESUMO

In-sensor multi-task learning is not only the key merit of biological visions but also a primary goal of artificial-general-intelligence. However, traditional silicon-vision-chips suffer from large time/energy overheads. Further, training conventional deep-learning models is neither scalable nor affordable on edge-devices. Here, a material-algorithm co-design is proposed to emulate human retina and the affordable learning paradigm. Relying on a bottle-brush-shaped semiconducting p-NDI with efficient exciton-dissociations and through-space charge-transport characteristics, a wearable transistor-based dynamic in-sensor Reservoir-Computing system manifesting excellent separability, fading memory, and echo state property on different tasks is developed. Paired with a 'readout function' on memristive organic diodes, the RC recognizes handwritten letters and numbers, and classifies diverse costumes with accuracies of 98.04%, 88.18%, and 91.76%, respectively (higher than all reported organic semiconductors). In addition to 2D images, the spatiotemporal dynamics of RC naturally extract features of event-based videos, classifying 3 types of hand gestures at an accuracy of 98.62%. Further, the computing cost is significantly lower than that of the conventional artificial-neural-networks. This work provides a promising material-algorithm co-design for affordable and highly efficient photonic neuromorphic systems.

19.
Sci Adv ; 8(44): eadd1980, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36322650

RESUMO

Using smart photochromic and luminescent tissues in camouflage/cloaking of natural creatures has inspired efforts to develop synthetic stimuli-responsive materials for data encryption and anticounterfeiting. Although many optical data-encryption materials have been reported, they generally require only one or a simple combination of few stimuli for decryptions and rarely offer output corruptibility that prevents trial-and-error attacks. Here, we report a series of multiresponsive donor-acceptor Stenhouse adducts (DASAs) with unprecedented switching behavior and controlled reversibility via diamine conformational locking and substrate free-volume engineering and their capability of sequential logic encryption (SLE). Being analogous to the digital circuits, the output of DASA gel-based data-encryption system depends not only on the present input stimulus but also on the sequence of past inputs. Incorrect inputs/sequences generate substantial fake information and lead attackers to the point of no return. This work offers new design concepts for advanced data-encryption materials that operate via SLE, paving the path toward advanced encryptions beyond digital circuit approaches.

20.
Front Nutr ; 9: 1001031, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407549

RESUMO

Placental function is vital to the fetal growth of sows, and resveratrol (RES) can protect cells against oxidative stress, which is one of the major factors impairing placental function. This study aimed to investigate the effect of dietary resveratrol (RES) on placental function and reproductive performance during late pregnancy in a sow model from the aspects of oxidative stress, insulin resistance, and gut microbiota. A total of 26 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into two groups (n = 13) and fed with a basal diet or a diet containing 200 mg/kg of resveratrol from day 85 of gestation until parturition. The dietary supplementation of RES increased the litter weight at parturition by 12.53% (p = 0.145), with ameliorated insulin resistance (HOMA-IR), increased triglyceride (TG) levels, and decreased interleukin (IL)-1ß and IL-6 levels in serum (p < 0.05). Moreover, resveratrol increased the placental vascular density (p < 0.05) with the enhanced expression of nutrient transporter genes (SLC2A1 and SLC2A3) and antioxidant genes, such as superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) but declined the expression of inflammatory genes, such as IL-1ß and IL-6 (p < 0.05). The characterization of the fecal microbiota revealed that resveratrol decreased the relative abundance of the Christensensllaceae R-7 group and Ruminococcaceae UCG-008 (p < 0.05), which had a positive linear correlation with the expression of IL-1ß and IL-6 (p < 0.05), but had a negative linear correlation with the expression of SOD2, HO-1, SLC2A1, and SCL2A3 genes (p < 0.05). These data demonstrated that dietary supplementation with resveratrol can improve placental function with ameliorated insulin resistance, oxidative stress, and inflammation potentially by regulating Ruminococcaceae UCG-008 and the Christensensllaceae R-7 group in sows.

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