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1.
Neural Regen Res ; 20(1): 209-223, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38767486

RESUMO

JOURNAL/nrgr/04.03/01300535-202501000-00029/figure1/v/2024-05-14T021156Z/r/image-tiff Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory. Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1; however, whether KIF21A modulates dendritic structure and function in neurons remains unknown. In this study, we found that KIF21A was distributed in a subset of dendritic spines, and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines. Furthermore, the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity. Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching, and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1, but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1. Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals' cognitive abilities. Taken together, our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

2.
Proc Natl Acad Sci U S A ; 121(18): e2314541121, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38657049

RESUMO

Recent evidence has demonstrated that the transsynaptic nanoscale organization of synaptic proteins plays a crucial role in regulating synaptic strength in excitatory synapses. However, the molecular mechanism underlying this transsynaptic nanostructure in inhibitory synapses still remains unclear and its impact on synapse function in physiological or pathological contexts has not been demonstrated. In this study, we utilized an engineered proteolysis technique to investigate the effects of acute cleavage of neuroligin-2 (NL2) on synaptic transmission. Our results show that the rapid cleavage of NL2 led to impaired synaptic transmission by reducing both neurotransmitter release probability and quantum size. These changes were attributed to the dispersion of RIM1/2 and GABAA receptors and a weakened spatial alignment between them at the subsynaptic scale, as observed through superresolution imaging and model simulations. Importantly, we found that endogenous NL2 undergoes rapid MMP9-dependent cleavage during epileptic activities, which further exacerbates the decrease in inhibitory transmission. Overall, our study demonstrates the significant impact of nanoscale structural reorganization on inhibitory transmission and unveils ongoing modulation of mature GABAergic synapses through active cleavage of NL2 in response to hyperactivity.


Assuntos
Moléculas de Adesão Celular Neuronais , Proteínas do Tecido Nervoso , Sinapses , Transmissão Sináptica , Animais , Camundongos , Moléculas de Adesão Celular Neuronais/metabolismo , Epilepsia/metabolismo , Epilepsia/fisiopatologia , Epilepsia/patologia , Hipocampo/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Proteólise , Receptores de GABA-A/metabolismo , Sinapses/metabolismo , Transmissão Sináptica/fisiologia
3.
Br J Haematol ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685577

RESUMO

Multiple myeloma (MM) is an incurable plasma cell cancer in the bone marrow. Immunomodulatory drugs, such as lenalidomide (LEN) and pomalidomide, are backbone agents in MM treatment, and LEN resistance is commonly seen in the MM clinic. In this study, we presented that heterogeneous nuclear ribonucleoprotein U (hnRNPU) affected MM resistance to LEN via the regulation of target mRNA translation. hnRNPULow MM cells exhibited upregulated CRBN and IKZF1 proteins, stringent IKZF1/3 protein degradation upon LEN addition and increased sensitivity to LEN. RNA pulldown assays and RNA electrophoretic mobility shift assays revealed that hnRNPU bound to the 3'-untranslated region of CRBN and IKZF1 mRNA. A sucrose gradient assay suggested that hnRNPU specifically regulated CRBN and IKZF1 mRNA translation. The competition of hnRNPU binding to its target mRNAs by small RNAs with hnRNPU-binding sites restored MM sensitivity to LEN. hnRNPU function in vivo was confirmed in an immunocompetent MM mouse model constructed by the inoculation of Crbn-humanized murine 5TGM1 cells into CrbnI391V/+ mice. Overall, this study suggests a novel mechanism of LEN sensitivity in which hnRNPU represses CRBN and IKZF1 mRNA translation.

4.
Int J Biol Macromol ; 264(Pt 1): 130563, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431018

RESUMO

Both sensing and removal of Hg(II) are important to environment and human health in view of the high toxicity and wide applications of mercury in industry. This study aims to develop a cellulose-based fluorescent aerogel for simultaneous Hg(II) sensing and removal via conveniently cross-linking two nanomaterials cellulose nanocrystals and bovine serum albumin-functionalized gold nanoclusters (BSA-AuNCs) with epichlorohydrin. The aerogel exhibited strong homogeneous red fluorescence at the non-edged regions under UV light due to highly dispersed BSA-AuNCs in it, and its fluorescence could be quenched by Hg(II). Through taking pictures with a smartphone, Hg(II) in the range of 0-1000 µg/L could be quantified with a detection limit of 12.7 µg/L. The sorption isotherm of Hg(II) by the aerogel followed Freundlich model with an equation of Qe = 0.329*Ce1/0.971 and a coefficient of 0.999. The maximum sorption capacity can achieve 483.21 mg/g for Hg(II), much higher than many reported sorbents. The results further confirmed Hg(II) strong sorption and sensitive detection are due to its complexation and redox reaction with the chemical groups in aerogels and its strong fluorescence quenching effect. Due to extensive sources and low cost, cellulose is potential to be developed into aerogels with multiple functions for sophisticated applications.


Assuntos
Mercúrio , Nanopartículas Metálicas , Humanos , Celulose , Nanopartículas Metálicas/química , Mercúrio/química , Corantes Fluorescentes/química , Ouro/química , Espectrometria de Fluorescência/métodos
5.
MycoKeys ; 102: 267-284, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463693

RESUMO

Species of Grifola are famous edible mushrooms and are deeply loved by consumers around the world. Most species of this genus have been described and recorded in Oceania, Europe and South America, with only Grifolafrondosa being recorded in Asia. In this study, two novel species of Grifola from southwestern China (Asia) are introduced. Macro and micromorphological characters are described. Grifolaedulissp. nov. present medium-size basidiomata with gray to gray-brown lobes upper surface, mostly tibiiform or narrowly clavate, rarely narrowly lageniform or ellipsoid chlamydospores, cuticle hyphae terminal segments slightly enlarged. Grifolasinensissp. nov. has white to grayish white lobes upper surface, mostly ellipsoid, rarely narrowly utriform chlamydospores, and broadly ellipsoid to ellipsoid basidiospores (4.6-7.9 × 3.0-5.9 µm). The two new species are supported by phylogenetic analyses of combined nuclear rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS) and ß-tubulin (TUBB). Moreover, the genetic distance between TUBB sequences of those specimen from GenBank was 1.76-1.9%. Thus, the conspecificity relationship of our specimens remains uncertain, and further specimens are required to conclusively confirm its identity.

6.
Chin Herb Med ; 16(1): 13-26, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38375043

RESUMO

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

7.
Materials (Basel) ; 17(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38399052

RESUMO

Nowadays, lithium-ion batteries are undoubtedly known as the most promising rechargeable batteries. However, these batteries face some big challenges, like not having enough energy and not lasting long enough, that should be addressed. Ternary Ni-rich Li[NixCoyMnz]O2 and Li[NixCoyAlz]O2 cathode materials stand as the ideal candidate for a cathode active material to achieve high capacity and energy density, low manufacturing cost, and high operating voltage. However, capacity gain from Ni enrichment is nullified by the concurrent fast capacity fading because of issues such as gas evolution, microcracks propagation and pulverization, phase transition, electrolyte decomposition, cation mixing, and dissolution of transition metals at high operating voltage, which hinders their commercialization. In order to tackle these problems, researchers conducted many strategies, including elemental doping, surface coating, and particle engineering. This review paper mainly talks about origins of problems and their mechanisms leading to electrochemical performance deterioration for Ni-rich cathode materials and modification approaches to address the problems.

8.
Pharmaceuticals (Basel) ; 17(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38399363

RESUMO

Currently, research predominantly focuses on evaluating clinical effects at specific time points while neglecting underlying patterns within the treatment process. This study aims to analyze the dynamic alterations in PANSS total scores and prolactin levels in patients with schizophrenia treated with risperidone, along with the influencing covariates. Using data from an 8-week randomized, double-blind, multicenter clinical trial, a population pharmacodynamic model was established for the PANSS total scores of and prolactin levels in patients treated with risperidone. The base model employed was the Emax model. Covariate selection was conducted using a stepwise forward inclusion and backward elimination approach. A total of 144 patients were included in this analysis, with 807 PANSS total scores and 531 prolactin concentration values. The PANSS total scores of the patients treated with risperidone decreased over time, fitting a proportionally parameterized sigmoid Emax model with covariates including baseline score, course of the disease, gender, plasma calcium ions, and lactate dehydrogenase levels. The increase in prolactin levels conformed to the ordinary Emax model, with covariates encompassing course of the disease, gender, weight, red blood cell count, and triglyceride levels. The impacts of the baseline scores and the course of the disease on the reduction of the PANSS scores, as well as the influence of gender on the elevation of prolactin levels, each exceeded 20%. This study provides valuable quantitative data regarding PANSS total scores and prolactin levels among patients undergoing risperidone treatment across various physiological conditions.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 311: 124010, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38340446

RESUMO

In this study, we aimed to synthesis of Fe-doping green fluorescent carbon dots (G-CDs) through the co-electrolysis of chrysoidine G and potassium ferrocyanide for Cr(VI) detection. The use of potassium ferrocyanide improves the quantum yield and sensing performance of G-CDs toward Cr(VI). The G-CDs have a maximum excitation wavelength of 308 nm and an emission wavelength of 510 nm. Comprehensive analyses including Raman, FT-IR, and XPS provided insights into the chemical structure and composition of the G-CDs. Under optimal conditions, G-CDs demonstrated concentration-dependent quenching upon interaction with Cr(VI). A linear relationship within the range of 0.25-100 µM was established with a calibration equation of ΔF/F0 = 0.005 + 0.015CCr(VI), yielding an R2 value of 0.996 and a limit of detection of 0.15 µM. The applicability of the G-CDs method was demonstrated by successful Cr(VI) detection in water samples with recovery rates ranging from 98.8 % to 100.1 % and relative standard deviation within 3.0 %. The fluorescence lifetime and Zeta potential measurements confirmed that the mechanism was via a static quenching process, while redox reaction, nanoparticle aggregation, and surface charge variation also played significant roles.

10.
Cancer Lett ; 580: 216486, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37984724

RESUMO

Multiple myeloma (MM) is an incurable haematological cancer. Selinexor is the first-in-class selective inhibitor of nuclear export (SINE) and was newly approved for the treatment of MM. Until now, very few studies have investigated selinexor resistance in MM. Heterogeneous nuclear ribonucleoprotein U (hnRNPU) is an RNA-binding protein and a component of hnRNP complexes. Here we found that hnRNPU regulates MM sensitivity to selinexor. Cell apoptosis assays were performed to compare selinexor-induced cell death in control knockdown (CTR-KD) and hnRNPU knockdown (hnR-KD) MM cells. HnRNPU knockdown-induced nuclear protein retention was examined by proteomics array. HnRNPU-conferred mRNA translation regulation was evaluated by sucrose gradient assay, RNA electrophoresis mobility shift assay, and RNA pull-down assay. We found that hnR-KD MM cells were more sensitive to selinexor-induced cell death in vitro and in mouse model. MM patients who responded to selinexor had relatively low hnRNPU expression. In brief, hnRNPU comprehensively regulated MM sensitivity to selinexor by affecting the localization of LTV1 and NMD3, and mRNA translation of MDM2 and RAN, which were involved in XPO1-mediated nuclear export of ribosome subunits and tumor suppressors. Our discoveries indicate that hnRNPU might be a possible marker to categorize MM patients for the use of Selinexor.


Assuntos
Mieloma Múltiplo , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Ribonucleoproteínas Nucleares Heterogêneas Grupo U , Hidrazinas/farmacologia , Carioferinas/genética , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , RNA , Proteínas de Ligação a RNA/genética
11.
Life Sci ; 333: 122157, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37805164

RESUMO

AIMS: This study aimed to investigate the effect and mechanism of methylcrotonyl-CoA carboxylase subunit 1 (MCCA) on multidrug resistance in multiple myeloma (MM). MATERIALS AND METHODS: The apoptosis kit and CCK-8 reagent were used to detect drug-induced cell apoptosis and viability. Immunoprecipitation, immunofluorescence staining, and protein structural simulation were used to detect the interaction between MCCA and Bad. Immunodeficient mice were injected with ARD cells and treated with bortezomib. Changes in tumor burden were recorded by bioluminescence imaging, and κ light chain content in the blood of mice was detected by enzyme-linked immunoassay. KEY FINDINGS: Patients with high MCCA expression from a primary MM dataset had superior overall survival. After treatment with different anti-MM drugs, MCCA knockdown MM (MCCA-KD) cells had higher survival rates than control knockdown (CTR-KD) cells (p < 0.05). Mechanistic studies have revealed that MCCA-KD cells had dysfunctional mitochondria with decreased Bax and Bad levels and increased Bcl-xl and Mcl-1 levels. Furthermore, that MCCA and Bad demonstrated protein-protein interactions. The half-life of Bad in MCCA-KD cells is significantly shorter than that in CTR-KD cells (7.34 vs. 2.42 h, p < 0.05). In a human MM xenograft mouse model, we confirmed that MCCA-KD tumors had a poor response to anti-MM drugs in vivo. Finally, we showed that MCCA might contribute to multidrug resistance in different human cancers, particularly in solid tumors. SIGNIFICANCE: Our findings demonstrated a novel function of MCCA in multidrug resistance. The lack of MCCA expression promoted antiapoptotic cell signaling in MM cells.


Assuntos
Mieloma Múltiplo , Humanos , Animais , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Acil Coenzima A/farmacologia , Acil Coenzima A/uso terapêutico , Bortezomib/farmacologia , Apoptose , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos
12.
J Agric Food Chem ; 71(41): 15186-15193, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37788677

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an ideal target for herbicide resistance genetic engineering. In this study, a mutant MFRR-2 with mesotrione resistance was screened from an Oryza sativa HPPD and mutant-Zea mays HPPD DNA shuffling library. The enzyme properties showed that although the stability of the mutant decreased in vitro, the enzyme activity of MFRR-2 at the optimum temperature of 25 °C was still equivalent to that of OsHPPD. Under 50 µM mesotrione treatment, MFRR-2 enzyme activity remained at approximately 90%, while the enzyme activity of OsHPPD decreased by approximately 50%. Surprisingly, Fe2+ was found to have an inhibitory effect on the enzyme activity. Then, the transgenic rice of the MFRR-2 gene showed approximately 1.5 times mesotrione resistance compared to OsHPPD transgenic rice. In conclusion, this study has conducted a beneficial exploration on the use of DNA shuffling for HPPD-directed evolution, and the mutant has potential application value for herbicide resistance genetic engineering.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase , Dioxigenases , Herbicidas , Oryza , Resistência a Herbicidas/genética , 4-Hidroxifenilpiruvato Dioxigenase/genética , Oryza/genética , Herbicidas/farmacologia , Embaralhamento de DNA , Inibidores Enzimáticos/farmacologia
13.
Chin Herb Med ; 15(3): 369-375, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37538863

RESUMO

Perilla frutescens, an annual herb of the Labiatae family, has been cultivated in China for more than 2000 years. P. frutescens is the one of the first medicinal and edible plant published by the Ministry of Health. Its leaves, stems and seeds can be used as medicine and edible food. Because of the abundant nutrients and bioactive components in this plant, P. frutescens has been studied extensively in medicine, food, health care and chemical fields with great prospects for development. This paper reviews the cultivation history, chemical compositions and pharmacological activities of P. frutescens, which provides a reference for the development and utilization of P. frutescens resources.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 301: 122947, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37295382

RESUMO

Monitoring hypochlorite levels in water is of great importance because of its high toxicity and wide applications as water disinfectants. In this manuscript, carbon dot (CD) was electrochemically prepared by using dopamine and epigallocatechin gallate (molar ratio 1:1) as the carbon source for efficient hypochlorite determination. By electrolyzing the solution at 10 V for 12 min with PBS as an electrolyte, dopamine would react with epigallocatechin at the anode, and through polymerization, dehydration, and carbonization, strong blue-fluorescent CDs were obtained. CDs were characterized by UV-Vis spectroscopy, fluorescence spectroscopy, high-resolution transmission electron microscopy, FT-IR, etc. These CDs have an excitation wavelength at 372 nm and an emission wavelength at 462 nm, owing an average particle size of 5.5 nm. The presence of hypochlorites can quench the fluorescence of CDs, and its reduction in intensity is linear with hypochlorite concentration over the range of 0.5-50 µM, ΔF/F0 = 0.0056 + 0.0194CClO-, R2=0.997. The detection limit achieved 0.23 µM (S/N = 3). The mechanism for fluorescence quenching is via a dynamic process. Different from many other fluorescence methods based on the strong oxidizing ability of hypochlorites, our method shows strong selectivity toward hypochlorites over other oxidizing agents such as H2O2. The assay was validated by the detection of hypochlorites in water samples, with recoveries between 98.2% and 104.3%.


Assuntos
Pontos Quânticos , Pontos Quânticos/química , Ácido Hipocloroso , Dopamina , Carbono/química , Peróxido de Hidrogênio , Espectroscopia de Infravermelho com Transformada de Fourier , Água , Corantes Fluorescentes/química
15.
Neuropeptides ; 101: 102355, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37390743

RESUMO

Visceral pain (VP) is caused by internal organ disease. VP is involved in nerve conduction and related signaling molecules, but its specific pathogenesis has not yet been fully elucidated. Currently, there are no effective methods for treating VP. The role of P2X2/3 in VP has progressed. After visceral organs are subjected to noxious stimulation, cells release ATP, activate P2X2/3, enhance the sensitivity of peripheral receptors and the plasticity of neurons, enhance sensory information transmission, sensitize the central nervous system, and play an important role in the development of VP. However, antagonists possess the pharmacological effect of relieving pain. Therefore, in this review, we summarize the biological functions of P2X2/3 and discuss the intrinsic link between P2X2/3 and VP. Moreover, we focus on the pharmacological effects of P2X2/3 antagonists on VP therapy and provide a theoretical basis for its targeted therapy.


Assuntos
Dor Visceral , Humanos , Neurônios , Sistema Nervoso Central , Transdução de Sinais , Trifosfato de Adenosina
16.
Chemistry ; 29(52): e202301469, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37385953

RESUMO

In this work, an organic-inorganic hybrid crystal, violet-crystal (VC), was used to etch the nickel foam (NF) to fabricate a self-standing electrode for the water oxidation reaction. The efficacy of VC-assisted etching manifests the promising electrochemical performance towards the oxygen evolution reaction (OER), requiring only ~356 and ~376 mV overpotentials to reach 50 and 100 mA cm-2 , respectively. The OER activity improvement is attributed to the collectively exhaustive effects arising from the incorporation of various elements in the NF, and the enhancement of active site density. Furthermore, the self-standing electrode is robust, exhibiting a stable OER activity after 4,000 cyclic voltammetry cycles, and ~50 h. The anodic transfer coefficients (αa ) show that the first electron transfer step is the rate-determining step on the surface of NF-VCs-1.0 (NF etched by 1 g of VCs) electrode, while the chemical step involving dissociation following the first electron transfer step is identified as the rate-limiting step in other electrodes. The lowest Tafel slope value observed in the NF-VCs-1.0 electrode indicates the high surface coverage of oxygen intermediates and more favorable OER reaction kinetics, as confirmed by high interfacial chemical capacitance and low charge transport/interfacial resistance. This work demonstrates the importance of VCs-assisted etching of NF to activate the OER, and the ability to predict reaction kinetics and rate-limiting step based on αa values, which will open new avenues to identify advanced electrocatalysts for the water oxidation reaction.

17.
Cancer Lett ; 565: 216218, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37149018

RESUMO

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Ivermectin is a US Food and Drug Administration-approved drug for antiparasitic use. Here, we showed that ivermectin exerted anti-MM effects and significantly synergized with proteasome inhibitors in vitro and in vivo. Ivermectin alone exhibited mild anti-MM activity in vitro. Further investigation suggested that ivermectin inhibited proteasome activity in the nucleus by repressing the nuclear import of proteasome subunits, such as PSMB5-7 and PSMA3-4. Therefore, ivermectin treatment caused the accumulation of ubiquitylated proteins and the activation of the UPR pathway in MM cells. Furthermore, ivermectin treatment caused DNA damage and DNA damage response (DDR) signaling pathway activation in MM cells. Ivermectin and bortezomib exhibited synergized anti-MM activity in vitro. The dual-drug treatment resulted in synergistic inhibition of proteasome activity and increased DNA damage. An in vivo study using a human MM cell line xenograft mouse model showed that ivermectin and bortezomib efficiently repressed MM tumor growth in vivo, while the dual-drug treatment was well tolerated by experimental animals. Overall, our results demonstrated that ivermectin alone or cotreated with bortezomib might be promising in MM treatment.


Assuntos
Antineoplásicos , Mieloma Múltiplo , Humanos , Animais , Camundongos , Inibidores de Proteassoma/farmacologia , Bortezomib/farmacologia , Mieloma Múltiplo/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Modelos Animais de Doenças , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
18.
Langmuir ; 39(15): 5495-5504, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37018471

RESUMO

Superhydrophobic coatings have garnered significant research interest due to their potential applications in areas such as ant-icing and windows. This study focuses on the development of superhydrophobic coatings using air-assisted electrospray and the effect of different carbon additives as templates in the coating. Carbon templates, with their unique topological varieties, offer a cost-effective alternative to other patterning technologies such as photolithography. By introducing dispersed carbon black, carbon nanotubes, and graphene additives in TEOS solution, silica is given the ability of localized secondary growth on or around the carbon surfaces as well as the building structure to provide adequate roughness on the substrate surface. The templated silica formations provide a thin coating with nano-scale roughness for heightened water resistance. As compared with the template-free coating that has small silica particles, a surface roughness of 135 nm, and a water contact angle (WCA) of 101.6° (non-superhydrophobic), the carbon templating effect allowed for increased silica particle size, a surface roughness as high as 845 nm, a WCA above 160°, and the ability to maintain superhydrophobicity over 30 abrasion cycles. The morphological characteristics that resulted from the templating effect correlate directly with heightened performance of the coatings. Herein, the carbon additives have been found to serve as cheap and effective templates for silica formation in thin TEOS-derived superhydrophobic coatings.

19.
J Cardiovasc Transl Res ; 16(5): 1220-1231, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36988860

RESUMO

Phosphoinositide-dependent protein kinase-1 (PDK1), a master kinase and involved in multiple signaling transduction, participates in regulating embryonic cardiac development and postnatal cardiac remodeling. Germline PDK1 knockout mice displayed no heart development; in this article, we deleted PDK1 in heart tissue with different cre to characterize the temporospatial features and find the relevance with congenital heart disease(CHD), furthermore to investigate the underlying mechanism. Knocking out PDK1 with Nkx2.5-cre, the heart showed prominent pulmonic stenosis. Ablated PDK1 with Mef2cSHF-cre, the second heart field (SHF) exhibited severe hypoplasia. And deleted PDK1 with αMHC-cre, the mice displayed dilated heart disease, protein analysis indicated PI3K and ERK were activated; meanwhile, PDK1-AKT-GSK3, and S6K-S6 were disrupted; phosphorylation level of Akt473, S6k421/424, and Gsk3α21 enhanced; however, Akt308, S6k389, and Gsk3ß9 decreased. In mechanism investigation, we found SHP2 membrane localization and phosphorylation level of SHP2542 elevated, which suggested SHP2 likely mediated the disruption.


Assuntos
Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Cardiopatias Congênitas , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Animais , Camundongos , Quinase 3 da Glicogênio Sintase/metabolismo , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Camundongos Knockout , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo
20.
Sci Rep ; 13(1): 2560, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36781922

RESUMO

In order to improve the functionality and additional value of agricultural products, this study developing nano-selenium fermentation broth and established a new application strategy of bio-nano-selenium by screening and identifying selenium-rich microorganisms. We isolated a new strain from tobacco waste and named it Bacillus subtilis SE201412 (GenBank accession no. OP854680), which could aerobically grow under the condition of 66,000 mg L-1 selenite concentration, and could convert 99.19% of selenite into biological nano-selenium (BioSeNPs) within 18 h. Using strain SE201412, we industrially produced the different concentrations of fermentation broth containing 5000-3000 mg L-1 pure selenium for commercial use. The synthesized selenium nanoparticles (SeNPs) were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). TEM and SEM results showed that SeNPs were distributed outside cells. NTA assay of fermentation broth indicated that the nanoparticles were spherical with an average particle size of 126 ± 0.5 nm. Toxicity test revealed that the median lethal dose (LD50) of the fermentation broth to mice was 2710 mg kg-1, indicating its low toxicity and high safety. In addition, we applied BioSeNP fermentation broth to rice and wheat through field experiments. The results showed that the application of fermentation broth significantly increased the total selenium content and organic selenium percentage in rice and wheat grains. Our findings provide valuable reference for the development of BioSeNPs with extensive application prospects.


Assuntos
Nanopartículas , Selênio , Animais , Camundongos , Bacillus subtilis , Fermentação , Ácido Selenioso
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