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1.
ACS Appl Mater Interfaces ; 16(19): 25065-25070, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38712510

RESUMO

Phase transition materials with switchable second-order nonlinear optical (NLO) properties have attracted extensive attention because of their great application potential in photoelectric switches, sensors, and modulators, while metal-free organics with NLO switchability near room temperature remain scarce. Herein, we report a hydrogen-bonded metal-free organic crystal, 2-methylpropan-2-aminium 2,2-dimethylpropanoate (1), exhibiting a room-temperature phase transition and favorable NLO switchability. Through investigations on its thermal anomalies, dielectric properties, and crystal structures, we uncover that 1 holds a near-room-temperature phase transition at 303 K from noncentrosymmetric point group C2v to centrosymmetric one D2h, which is attributed to the order-disorder transformations of both tert-butylamine cations and dimethylpropionic acid anions. Accompanied by symmetry change during the phase transition, 1 exhibits reversible and repeatable NLO "on-off" switchability with a desirable switching contrast ratio of ca. 19 between high and low NLO states. This discovery demonstrates a metal-free organic crystal with NLO switching behavior near room temperature, serving as a promising candidate in smart and ecofriendly photoelectric functional materials and devices.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38770712

RESUMO

Herein, we present a novel ultrasensitive graphene field-effect transistor (GFET) biosensor based on lithium niobate (LiNbO3) ferroelectric substrate for the application of breast cancer marker detection. The electrical properties of graphene are varied under the electrostatic field, which is generated through the spontaneous polarization of the ferroelectric substrate. It is demonstrated that the properties of interface between graphene and solution are also altered due to the interaction between the electrostatic field and ions. Compared with the graphene field-effect biosensor based on the conventional Si/SiO2 gate structure, our biosensor achieves a higher sensitivity to 64.7 mV/decade and shows a limit of detection down to 1.7 fM (equivalent to 12 fg·mL-1) on the detection of microRNA21 (a breast cancer marker). This innovative design combining GFETs with ferroelectric substrates holds great promise for developing an ultrahigh-sensitivity biosensing platform based on graphene that enables rapid and early disease diagnosis.

3.
J Diabetes ; 16(6): e13557, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751366

RESUMO

Diabetes mellitus (DM) is a common chronic disease affecting humans globally. It is characterized by abnormally elevated blood glucose levels due to the failure of insulin production or reduction of insulin sensitivity and functionality. Insulin and glucagon-like peptide (GLP)-1 replenishment or improvement of insulin resistance are the two major strategies to treat diabetes. Recently, optogenetics that uses genetically encoded light-sensitive proteins to precisely control cell functions has been regarded as a novel therapeutic strategy for diabetes. Here, we summarize the latest development of optogenetics and its integration with synthetic biology approaches to produce light-responsive cells for insulin/GLP-1 production, amelioration of insulin resistance and neuromodulation of insulin secretion. In addition, we introduce the development of cell encapsulation and delivery methods and smart bioelectronic devices for the in vivo application of optogenetics-based cell therapy in diabetes. The remaining challenges for optogenetics-based cell therapy in the clinical translational study are also discussed.


Assuntos
Diabetes Mellitus , Optogenética , Humanos , Optogenética/métodos , Diabetes Mellitus/terapia , Animais , Insulina/metabolismo , Resistência à Insulina , Peptídeo 1 Semelhante ao Glucagon , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células Secretoras de Insulina/metabolismo
4.
Science ; 384(6695): 557-563, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38696573

RESUMO

Hydrogels are an attractive category of biointerfacing materials with adjustable mechanical properties, diverse biochemical functions, and good ionic conductivity. Despite these advantages, their application in electronics has been restricted because of their lack of semiconducting properties, and they have traditionally only served as insulators or conductors. We developed single- and multiple-network hydrogels based on a water-soluble n-type semiconducting polymer, endowing conventional hydrogels with semiconducting capabilities. These hydrogels show good electron mobilities and high on/off ratios, enabling the fabrication of complementary logic circuits and signal amplifiers with low power consumption and high gains. We demonstrate that hydrogel electronics with good bioadhesive and biocompatible interface can sense and amplify electrophysiological signals with enhanced signal-to-noise ratios.

5.
Sci Adv ; 10(14): eadk0647, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38569023

RESUMO

Conjugated polymers have demonstrated promising optoelectronic properties, but their brittleness and poor mechanical characteristics have hindered their fabrication into durable fibers and textiles. Here, we report a universal approach to continuously producing highly strong, ultratough conjugated polymer fibers using a flow-enhanced crystallization (FLEX) method. These fibers exhibit one order of magnitude higher tensile strength (>200 megapascals) and toughness (>80 megajoules per cubic meter) than traditional semiconducting polymer fibers and films, outperforming many synthetic fibers, ready for scalable production. These fibers also exhibit unique strain-enhanced electronic properties and exceptional performance when used as stretchable conductors, thermoelectrics, transistors, and sensors. This work not only highlights the influence of fluid mechanical effects on the crystallization and mechanical properties of conjugated polymers but also opens up exciting possibilities for integrating these functional fibers into wearable electronics.

6.
FASEB J ; 38(7): e23587, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38568835

RESUMO

Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut-metabolism-mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum. Plasma analysis revealed significantly higher levels of L-isoleucine and cholic acid along with 7-ketodeoxycholic acid. Mammary tissue showed elevated levels of arachidonic acid metabolites and norlithocholic acid. Proteomic analysis showed increased levels of IFIH1, Tnfaip8l2, IRGM, and IRF5 in mastitis rats, which suggests that mastitis triggers an inflammatory response and immune stress. Follistatin (Fst) and progesterone receptor (Pgr) were significantly downregulated, raising the risk of breast cancer. Extracellular matrix (ECM) receptors and focal adhesion signaling pathways were downregulated, while blood-milk barrier integrity was disrupted. Analysis of protein-metabolic network regulation revealed that necroptosis, protein digestion and absorption, and arachidonic acid metabolism were the principal regulatory pathways involved in the development of mastitis. In short, the onset of mastitis leads to changes in the microbiota and alterations in the metabolic profiles of various biological samples, including colonic contents, plasma, and mammary tissue. Key manifestations include disturbances in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism. At the same time, the integrity of the blood-milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.


Assuntos
Mastite , Infecções Estafilocócicas , Feminino , Humanos , Ratos , Animais , Staphylococcus aureus/fisiologia , Proteômica , Ácido Araquidônico/metabolismo , Mastite/microbiologia , Mastite/patologia , Mastite/veterinária , Inflamação/metabolismo , Redes e Vias Metabólicas , Glândulas Mamárias Animais/metabolismo , Infecções Estafilocócicas/metabolismo
7.
Nano Lett ; 24(15): 4691-4701, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38588212

RESUMO

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Imunoterapia , Radioimunoterapia , Glucose , Glucose Oxidase , Imunossupressores , Ácido Láctico , Neoplasias/terapia , Linhagem Celular Tumoral
8.
J Affect Disord ; 355: 459-469, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38580035

RESUMO

BACKGROUND: The aim of this study was to investigate the diagnostic value of ML techniques based on sMRI or/and fMRI for ADHD. METHODS: We conducted a comprehensive search (from database creation date to March 2024) for relevant English articles on sMRI or/and fMRI-based ML techniques for diagnosing ADHD. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), summary receiver operating characteristic (SROC) curve and area under the curve (AUC) were calculated to assess the diagnostic value of sMRI or/and fMRI-based ML techniques. The I2 test was used to assess heterogeneity and the source of heterogeneity was investigated by performing a meta-regression analysis. Publication bias was assessed using the Deeks funnel plot asymmetry test. RESULTS: Forty-three studies were included in the systematic review, 27 of which were included in our meta-analysis. The pooled sensitivity and specificity of sMRI or/and fMRI-based ML techniques for the diagnosis of ADHD were 0.74 (95 % CI 0.65-0.81) and 0.75 (95 % CI 0.67-0.81), respectively. SROC curve showed that AUC was 0.81 (95 % CI 0.77-0.84). Based on these findings, the sMRI or/and fMRI-based ML techniques have relatively good diagnostic value for ADHD. LIMITATIONS: Our meta-analysis specifically focused on ML techniques based on sMRI or/and fMRI studies. Since EEG-based ML techniques are also used for diagnosing ADHD, further systematic analyses are necessary to explore ML methods based on multimodal medical data. CONCLUSION: sMRI or/and fMRI-based ML technique is a promising objective diagnostic method for ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Curva ROC , Aprendizado de Máquina
10.
J Clin Neurosci ; 124: 73-77, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38669904

RESUMO

OBJECTIVES: Few studies on ischemic complications and flow changes after a flow diverter covering the anterior cerebral artery. The purpose of the study was to explore the ischemic complications and anatomical alterations associated with the flow diverter after it covers the anterior cerebral artery. MATERIALS AND METHODS: In this single-center study, patients treated with FD covering the anterior cerebral artery at the First Affiliated Hospital of Zhengzhou University were retrospectively collected. The primary endpoint was ischemic complications related to the anterior cerebral artery. Secondary endpoints were anatomical changes in the anterior cerebral artery postoperatively and at follow-up. RESULTS: A total of 59 patients were included in this study. Four (6.8%) patients presented with ischemic stroke symptoms. Immediately after the procedure, complete occlusion of A1 and decreased blood flow was observed in 13 (22.0%) and 21 patients (35.6%), respectively. At follow-up, A1 artery was occluded in 34 patients (57.6%) and decreased blood flow was observed in 10 patients (16.9%). Symptoms of neurological deficits related to the anterior cerebral artery were not observed in all patients at follow-up. CONCLUSION: Coverage of A1 is safe, with a low incidence of ischemic stroke, when using an FD to treat aneurysms. Risk of reduced perfusion of the anterior cerebral artery postoperatively even if the anterior communicating artery is open. In cases with A1 occlusion, the blood flow in the distal the anterior cerebral artery can be adequately compensated by opening the anterior communicating artery and good vascular anastomoses.


Assuntos
Artéria Cerebral Anterior , Humanos , Masculino , Feminino , Artéria Cerebral Anterior/cirurgia , Artéria Cerebral Anterior/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Aneurisma Intracraniano/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Seguimentos , Circulação Cerebrovascular/fisiologia
11.
Front Nutr ; 11: 1359989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646105

RESUMO

Introduction: With improvements in living conditions, modern individuals exhibit a pronounced inclination towards a high-fat diet, largely because of its distinctive gustatory appeal. However, the association between high-fat diets and metabolic complications has largely been ignored, and metabolic diseases such as obesity and non-alcoholic fatty liver disease now constitute a major public health concern. Because high-fat diets increase the risk of metabolic diseases, a thorough investigation into the impact of high-fat diets on gut microbiota and metabolism is required. Methods: We utilize 16S rRNA sequencing and untargeted metabolomics analysis to demonstrate that SD rats fed a high-fat diet exhibited marked alterations in gut microbiota and plasma, intestinal metabolism. Results: Changes in gut microbiota included a decreased abundance at phylum level for Verrucomicrobiota, and a decreased abundance at genus level for Akkermansia, Ralstonia, Bacteroides, and Faecalibacterium. Additionally, significant changes were observed in both intestinal and plasma metabolite levels, including an upregulation of bile acid metabolism, an upregulation of glucose-lipid metabolism, and increased levels of metabolites such as norlithocholic acid, cholic acid, D-fructose, D-mannose, fructose lactate, and glycerophosphocholine. We also investigated the correlations between microbial communities and metabolites, revealing a significant negative correlation between Akkermansia bacteria and cholic acid. Discussion: Overall, our findings shed light on the relationship between symbiotic bacteria associated with high-fat diets and metabolic biomarkers, and they provide insights for identifying novel therapeutic approaches to mitigate disease risks associated with a high-fat diet.

12.
Cell Signal ; 120: 111194, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38685520

RESUMO

Inositol Polyphosphate-5-Phosphatase J (INPP5J), a 5-phosphatase, has been identified as a tumor suppressor in several types of cancer. However, its role in pancreatic cancer (PC) is unknown. We found that the INPP5J expression was markedly lower in PC tissues (n = 50) compared to paired adjacent non-tumor tissues, and the lower INPP5J expression was relevant to a worse prognosis of PC patients. We thus proposed that INPP5J might inhibit PC progression and conducted gain-of- and loss-of-function experiments to test our hypothesis. Our results showed that overexpression of INPP5J inhibited cell proliferation, invasion, migration, and xenografted tumor of PC cells. INPP5J silencing showed the opposite effect. Pellino E3 Ubiquitin Protein Ligase 1 (PELI1) is one of the ubiquitin ligases known to promote ubiquitination of its downstream targets. We found that PELI1 could interact with INPP5J and promote the ubiquitination and degradation of INPP5J. PELI1 overexpression enhanced malignant behaviors of PC cells. However, INPP5J overexpression restored the alterations caused by PELI1 overexpression. In conclusion, the results suggest that the decreased INPP5J expression, caused by PELI1 through ubiquitination, may promote PC progression. The PELI1-INPP5J axis represents a potential therapeutic targetable node for PC.

13.
Natl Sci Rev ; 11(3): nwae039, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38549713

RESUMO

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer (CRC) cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione (GSH) via the upregulation of RRM2B-a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3'UTR of RRM2B increased its mRNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence (CDS) of OPA1-an essential GTPase protein for mitochondrial inner membrane fusion-also increased mRNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

14.
Materials (Basel) ; 17(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38541518

RESUMO

The Co3O4 is a typical p-type metal oxide semiconductor (MOS) that attracted great attention for hydrogen detection. In this work, porous, urchin-like Co3O4 was synthesized using a hydrothermal method with the assistance of glucose and a subsequent calcination process. Urchin-like Co3O4 has a large specific surface area of 81.4 m2/g. The response value of urchin-like Co3O4 to 200 ppm hydrogen at 200 °C is 36.5 (Rg/Ra), while the low-detection limit is as low as 100 ppb. The obtained Co3O4 also exhibited good reproducibility, long-term stability, and selectivity towards various gases (e.g., ammonia, hydrogen, carbon monoxide, and methane). Porous, urchin-like Co3O4 is expected to become a potential candidate for low-concentration hydrogen-sensing materials with the above advantages.

15.
J Hazard Mater ; 470: 134134, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38554514

RESUMO

Microbial remediation of cadmium-contaminated soil offers advantages like environmental friendliness, cost-effectiveness, and simple operation. However, the efficacy of this remediation process relies on obtaining dominant strains and a comprehensive understanding of their Cd adsorption mechanisms. This study identified two Cd-resistant bacteria, Burkholderia sp. 1-22 and Bacillus sp. 6-6, with significant growth-promoting effects from rice rhizosphere soil. The strains showed remarkable Cd resistance up to ∼200 mg/L and alleviated Cd toxicity by regulating pH and facilitating bacterial adsorption of Cd. FTIR analysis showed crucial surface functional groups, like carboxyl and amino groups, on bacteria played significant roles in Cd adsorption. The strains could induce CdCO3 formation via a microbially induced calcium precipitation (MICP) mechanism, confirmed by SEM-EDS, X-ray analysis, and elemental mapping. Pot experiments showed these strains significantly increased organic matter and enzyme activity (e.g., urease, sucrase, peroxidase) in the rhizosphere soil versus the control group. These changes are crucial for restricting Cd mobility. Furthermore, strains 6-6 and 1-22 significantly enhance plant root detoxification of Cd, alleviating toxicity. Notably, increased pH likely plays a vital role in enhancing Cd precipitation and adsorption by strains, converting free Cd into non-bioavailable forms.


Assuntos
Bacillus , Burkholderia , Cádmio , Oryza , Rizosfera , Microbiologia do Solo , Poluentes do Solo , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Cádmio/toxicidade , Cádmio/metabolismo , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Burkholderia/metabolismo , Adsorção , Bacillus/metabolismo , Biodegradação Ambiental , Concentração de Íons de Hidrogênio , Raízes de Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo
16.
Front Immunol ; 15: 1333850, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487532

RESUMO

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, with early metastasis and high recurrence. Since therapeutic options are limited, ES-SCLC has a characteristically short survival period and extremely poor prognosis. A combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs can achieve promising efficacy and safety in patients with ES-SCLC as a second-line or subsequent treatment, extending survival to some extent. However, the clinical outcomes remain mostly unsatisfactory and are sometimes affected by treatment-related adverse events. Case presentation: A 57-year-old woman with ES-SCLC was administered a combination therapy of atezolizumab (a PD-L1 inhibitor) and anlotinib [an oral multi-targeted tyrosine kinase inhibitor (TKI)]. She survived for 22 months, with no disease progression during the 28 courses of therapy. Unexpectedly, despite having no history of asthma, the patient developed asthma while receiving this regimen. This is possibly related to T-cell activation and the tumor immune microenvironment, which induce allergic inflammation after PD-L1 blockade. Conclusions: This is the first report of an asthma-negative ES-SCLC patient who developed asthma after receiving atezolizumab plus anlotinib. Although this combination therapy may effectively extend survival in SCLC patients, asthmatic symptoms should be closely monitored.


Assuntos
Anticorpos Monoclonais Humanizados , Asma , Indóis , Neoplasias Pulmonares , Quinolinas , Carcinoma de Pequenas Células do Pulmão , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Terapia Combinada , Asma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Microambiente Tumoral
17.
Biochem Genet ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438779

RESUMO

Liver cirrhosis can cause disturbances in blood circulation in the liver, resulting in impaired portal blood flow and ultimately increasing portal venous pressure. Portal hypertension induces portal-systemic collateral formation and fatal complications. Extrahepatic angiogenesis plays a crucial role in the development of portal hypertension. Curcumol is a sesquiterpenoid derived from the rhizome of Curcumae Rhizoma and has been confirmed to alleviate liver fibrosis by inhibiting angiogenesis. Therefore, our study was designed to explore the effects of curcumol on extrahepatic angiogenesis and portal hypertension. To induce cirrhosis, Sprague Dawley rats underwent bile duct ligation (BDL) surgery. Rats received oral administration with curcumol (30 mg/kg/d) or vehicle (distilled water) starting on day 15 following surgery, when BDL-induced liver fibrosis had developed. The effect of curcumol was assessed on day 28, which is the typical time of BDL-induced cirrhosis. The results showed that curcumol markedly reduced portal pressure in cirrhotic rats. Curcumol inhibited abnormal splanchnic inflow, mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting in cirrhotic rats. These protective effects were partially attributed to the inhibition on mesenteric angiogenesis by curcumol. Mechanically, curcumol partially reversed the BDL-induced activation of the JAK2/STAT3 signaling pathway in cirrhotic rats. Collectively, curcumol attenuates portal hypertension in liver cirrhosis by suppressing extrahepatic angiogenesis through inhibiting the JAK2/STAT3 signaling pathway.

18.
FASEB J ; 38(7): e23581, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38551642

RESUMO

Human DEAD/H box RNA helicase DDX6 acts as an oncogene in several different types of cancer, where it participates in RNA processing. Nevertheless, the role of DDX6 in pancreatic cancer (PC), together with the underlying mechanism, has yet to be fully elucidated. In the present study, compared with adjacent tissues, the level of DDX6 was abnormally increased in human PC tissues, and this increased level of expression was associated with poor prognosis. Furthermore, the role of DDX6 in PC was investigated by overexpressing or silencing the DDX6 in the PC cell lines, SW1990 and PaTu-8988t. A xenograft model was established by injecting nude mice with either DDX6-overexpressing or DDX6-silenced SW1990 cells. DDX6 overexpression promoted the proliferation and cell cycle transition, inhibited the cell apoptosis of PC cells, and accelerated tumor formation, whereas DDX6 knockdown elicited the opposite effects. DDX6 exerted positive effects on PC. RNA immunoprecipitation assay showed that DDX6 bound to kinesin family member C1 (KIFC1) mRNA, which was further confirmed by RNA pull-down assay. These results suggested that DDX6 positively regulated the expression of KIFC1. KIFC1 overexpression enhanced the proliferative capability of PC cells with DDX6 knockdown and inhibited their apoptosis. By contrast, DDX6 overexpression reversed the inhibitory effect of KIFC1 silencing on tumor proliferation. Subsequently, the transcription factor Yin Yang 1 (YY1) was shown to negatively regulate DDX6 at both the mRNA and protein levels. Dual-luciferase reporter assay verified that YY1 targeted the promoter of DDX6 and inhibited its transcription. High expression levels of YY1 decreased the proliferation of PC cells and promoted cell apoptosis, although these effects were reversed by DDX6 overexpression. Taken together, YY1 may target the DDX6/KIFC1 axis, thereby negatively regulating its expression, leading to an inhibitory effect on pancreatic tumor.


Assuntos
RNA Helicases DEAD-box , MicroRNAs , Neoplasias Pancreáticas , Fator de Transcrição YY1 , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
19.
Thromb Haemost ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38325399

RESUMO

INTRODUCTION: Platelets link thrombosis and inflammation, but how platelets handle the endogenous intraplatelet inflammatory machinery is less well understood. NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) is the central component of the interleukin (IL)-1-producing inflammasome. Elucidating the cell type-specific mechanism of NLRP3 in platelets may improve our understanding of thrombotic diseases. METHODS: Ferric chloride-induced mesenteric arteriole thrombosis models, tail bleeding models, and microfluidic whole-blood perfusion were used to study thrombosis and hemostasis. Additionally, we utilized aggregometry, flow cytometry, immunoprecipitation, and western blotting to investigate glycoprotein (GP)Ib-IX-mediated platelet function and signaling. RESULTS: NLRP3-/- mice exhibited severely impaired thrombosis and hemostasis, whereas apoptosis-associated speck-like protein containing a CARD (ASC)-/-, caspase-1-/-, and Nlrp3 A350V/+ CrePF4 mice did not exhibit such changes. NLRP3-/- platelets exhibited reduced adhesion to injured vessel walls and collagen and impaired von Willebrand factor (vWF)-dependent translocation and rolling behavior. NLRP3 deficiency decreased botrocetin-induced platelet aggregation and the phosphorylation of key signaling molecules in the GPIb-IX pathway. Mechanistically, decreased cAMP/PKA activity led to reduced phosphorylation of NLRP3, thereby enabling the interaction between NLRP3 and filamin A. This interaction accelerated the dissociation of filamin A from GPIbα, which allowed a 14-3-3ζ-dependent increase in GPIb-IX affinity to vWF. Finally, platelet NLRP3 was found to largely regulate thrombotic disease models, such as models of stroke and deep vein thrombosis. CONCLUSION: NLRP3 promoted the function of the major platelet adhesion receptor GPIb-IX without involving NLRP3 inflammasome assembly or IL-1ß production.

20.
Adv Mater ; 36(19): e2312650, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38339884

RESUMO

Optical grating devices based on micro/nanostructured functional surfaces are widely employed to precisely manipulate light propagation, which is significant for information technologies, optical data storage, and light sensors. However, the parameters of rigid periodic structures are difficult to tune after manufacturing, which seriously limits their capacity for in situ light manipulation. Here, a novel anti-eavesdropping, anti-damage, and anti-tamper dynamic optical encryption strategy are reported via tunable mechanical composite wrinkle micrograting encryption systems (MCWGES). By mechanically composing multiple in-situ tunable ordered wrinkle gratings, the dynamic keys with large space capacity are generated to obtain encrypted diffraction patterns, which can provide a higher level of security for the encrypted systems. Furthermore, a multiple grating cone diffraction model is proposed to reveal the dynamic optical encryption principle of MCWGES. Optical encryption communication using dynamic keys has the effect of preventing eavesdropping, damage, and tampering. This dynamic encryption method based on optical manipulation of wrinkle grating demonstrates the potential applications of micro/nanostructured functional surfaces in the field of information security.

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