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1.
Adv Mater ; : e2401392, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821489

RESUMO

Anatomizing mixed-phases, referring to analyzing the mixing profiles and quantifying the phases' proportions in a material, which is of great significance in the genuine applications. Here, by using second-harmonic generation (SHG) polarimetry and piezoresponse force microscopy (PFM) techniques, this work elucidates the contributions and distributions of two different symmetric phases mixed in an archetype monoaxial molecular ferroelectric, diisopropylammonium chloride (DIPACl). The two competing phases are preferred in thermodynamics or kinetic process respectively, and this work evidences the switching behavior between the two competing phases facilitated by an external electrical field as opposed to a heating process. This research contributes novel insights into phase engineering in the field of molecular ferroelectrics and is poised to serve as a potent analytical tool for subsequent applications.

2.
Chem Soc Rev ; 53(11): 5781-5861, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38690681

RESUMO

Ferroelectricity, which has diverse important applications such as memory elements, capacitors, and sensors, was first discovered in a molecular compound, Rochelle salt, in 1920 by Valasek. Owing to their superiorities of lightweight, biocompatibility, structural tunability, mechanical flexibility, etc., the past decade has witnessed the renaissance of molecular ferroelectrics as promising complementary materials to commercial inorganic ferroelectrics. Thus, on the 100th anniversary of ferroelectricity, it is an opportune time to look into the future, specifically into how to push the boundaries of material design in molecular ferroelectric systems and finally overcome the hurdles to their commercialization. Herein, we present a comprehensive and accessible review of the appealing development of molecular ferroelectrics over the past 10 years, with an emphasis on their structural diversity, chemical design, exceptional properties, and potential applications. We believe that it will inspire intense, combined research efforts to enrich the family of high-performance molecular ferroelectrics and attract widespread interest from physicists and chemists to better understand the structure-function relationships governing improved applied functional device engineering.

3.
Sci Rep ; 14(1): 11002, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745014

RESUMO

The recommended bearing capacity of medium weathering mudstone foundation is less than the capacity of the rock structure to withstand loads in Southwest China. A comprehensive failure characterization of medium weathering mudstone in Chengdu has been performed including bearing plate test (BPT), binocular vision measurement (BVM) test, uniaxial compressive strength test, trial trench test of shallow rock surface and 3D imaging in this paper. Failure behavior of rock has been modeled with 3D imaging algorithm that utilizes Zhang's calibration method in BVM system combination with trial trench test of shallow rock surface. The bearing capacity of medium weathering mudstone foundation were extracted from uniaxial experiments and BPT-BVM test by fitting relevant material properties to the data. The results revealed that: Bearing capacity of medium weathering mudstone of layered isotropic in Chengdu is undervalued. Specifically, the characteristic load carrying value is in the range 1500-2500 kP, that is 50% higher than in the local standard system. Failure process is different from Hoek-Brown Failure Criterion, presenting a wave peak transfer phenomenon of the increment displacement into the distance. Thus, it can be reduced to that of punching failures for thin bedded structures of Moudstone foundations. Compressive strength of soft rock proves to be main factor limiting the bearing capacity, a clear correlation between the uniaxial compressive strength reduction coefficient and the bearing capacity has been used to establish, leading to the proposal of a load bearing capacity prediction model.

4.
Adv Sci (Weinh) ; : e2400636, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778554

RESUMO

Over the past years, the application potential of ferroelectric nanomaterials with unique physical properties for modern electronics is highlighted to a large extent. However, it is relatively challenging to fabricate inorganic ferroelectric nanomaterials, which is a process depending on a vacuum atmosphere at high temperatures. As significant complements to inorganic ferroelectric nanomaterials, the nanomaterials of molecular ferroelectrics are rarely reported. Here a low-cost room-temperature antisolvent method is used to synthesize free-standing 2D organic-inorganic hybrid perovskite (OIHP) ferroelectric nanosheets (NSs), that is, (CHA)2PbBr4 NSs (CHA = cyclohexylammonium), with an average lateral size of 357.59 nm and a thickness ranging from 10 to 70 nm. This method shows high repeatability and produces NSs with excellent crystallinity. Moreover, ferroelectric domains in single NSs can be clearly visualized and manipulated using piezoresponse force microscopy (PFM). The domain switching and PFM-switching spectroscopy indicate the robust in-plane ferroelectricity of the NSs. This work not only introduces a feasible, low-cost, and scalable method for preparing molecular ferroelectric NSs but also promotes the research on molecular ferroelectric nanomaterials.

5.
Nat Commun ; 15(1): 4470, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796520

RESUMO

Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (Tc) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a Tc value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high Tc and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-Tc ferroelectrics with various physical properties.

6.
Cell Mol Biol (Noisy-le-grand) ; 70(1): 40-45, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38372116

RESUMO

The purpose of this study was to explore the differential expression of Pax3, Rad51 and VEGF-C in esophageal gastric junction adenocarcinoma and distal gastric adenocarcinoma and their relationship with cancer occurrence and development. 57 patients with gastric cancer were included and divided into esophageal gastric junction adenocarcinoma group (n=28) and distal gastric adenocarcinoma group (n=29). The positive expressions of Pax3, Rad51 and VEGF-C in the control group were lower than those in the esophageal gastric junction adenocarcinoma group and distal gastric adenocarcinoma group respectively (P<0.05). In esophageal gastric junction adenocarcinoma with low differentiation, positive expressions of Pax3, Rad51, and VEGF-C surpassed those in high/medium differentiation (P<0.05). Serosa-infiltrated cases exhibited higher Pax3 and Rad51 expressions compared to non-infiltrated cases (P<0.05). Rad51 and VEGF-C positivity were notably elevated in cases with lymph node metastasis compared to those without (P<0.05). Distal gastric adenocarcinoma displayed higher VEGF expression than middle/low differentiated adenocarcinomas. Rad51 expression was significantly higher in women than in men (P<0.05). The positive rates of Pax3, Rad51, and VEGF-C were markedly increased in esophageal gastric junction adenocarcinoma and distal gastric adenocarcinoma compared to normal gastric tissue, and these were associated with the degree of differentiation, depth of invasion, and lymph node metastasis in patients. Particularly, Rad51 exhibited a positive correlation with cancer cell differentiation, invasion depth, and lymph node metastasis in cancer tissue.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Fator de Transcrição PAX3 , Rad51 Recombinase , Neoplasias Gástricas , Fator C de Crescimento do Endotélio Vascular , Feminino , Humanos , Masculino , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Metástase Linfática , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Fatores de Transcrição , Fator C de Crescimento do Endotélio Vascular/genética , Fator de Transcrição PAX3/genética , Rad51 Recombinase/genética
7.
Adv Mater ; 36(11): e2307518, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38041802

RESUMO

On the path of persisting Moore's Law, one of the biggest obstacles is the "Boltzmann tyranny," which defines the lower limit of power consumption of individual transistors. Negative capacitance (NC) in ferroelectrics could provide a solution and has garnered significant attention in the fields of nanoelectronics, materials science, and solid-state physics. Molecular ferroelectrics, as an integral part of ferroelectrics, have developed rapidly in terms of both performance and functionality, with their inherent advantages such as easy fabrication, mechanical flexibility, low processing temperature, and structural tunability. However, studies on the NC in molecular ferroelectrics are limited. In this study, the focus is centered on the fabricated high-quality thin films of trimethylchloromethyl ammonium trichlorocadmium(II), and a pioneering investigation on their NC responses is conducted. The findings demonstrate that the NC exhibited by molecular ferroelectrics is comparable to that of conventional HfO2 -based ferroelectrics. This underscores the potential of molecular material systems for next-generation electronic devices.

8.
Adv Sci (Weinh) ; 11(4): e2305016, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38037482

RESUMO

With outstanding advantages of chemical synthesis, structural diversity, and mechanical flexibility, molecular ferroelectrics have attracted increasing attention, demonstrating themselves as promising candidates for next-generation wearable electronics and flexible devices in the film form. However, it remains a challenge to grow high-quality thin films of molecular ferroelectrics. To address the above issue, a volume-confined method is utilized to achieve ultrasmooth single-crystal molecular ferroelectric thin films at the sub-centimeter scale, with the thickness controlled in the range of 100-1000 nm. More importantly, the preparation method is applicable to most molecular ferroelectrics and has no dependency on substrates, showing excellent reproducibility and universality. To demonstrate the application potential, two-dimensional (2D) transitional metal dichalcogenide semiconductor/molecular ferroelectric heterostructures are prepared and investigated by optical spectroscopic method, proving the possibility of integrating molecular ferroelectrics with 2D layered materials. These results may unlock the potential for preparing and developing high-performance devices based on molecular ferroelectric thin films.

9.
Materials (Basel) ; 16(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38067992

RESUMO

In this work, the long-term skid resistance attenuation law of asphalt mixtures in the presence of aeolian sand was studied. Four types of asphalt mixtures underwent skid resistance abrasion tests using an accelerated loading tester. The pendulum value (BPN) and structure depth (MTD) of these four mixtures were determined under various conditions of sand density and abrasion times. The correlation between the BPN and density and the number of times of abrasion were investigated, respectively, to analyze the skid resistance attenuation law at the microscopic and macroscopic levels. Our results indicate that the skid resistance of the four types of asphalt mixtures initially decreased and subsequently reached a stable state. Sand density primarily influences skid resistance during the initial stage, while the number of abrasions becomes the dominant factor affecting skid resistance in the later stages.

10.
Nano Lett ; 23(16): 7419-7426, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37539988

RESUMO

Multifarious molecular ferroelectrics with multipolar axial characteristics have emerged in recent years, enriching the scenarios for energy harvesting, sensing, and information processing. The increased polar axes have enhanced the urgency of distinguishing different polarization states in material design, mechanism exploration, etc. However, conventional methods hardly meet the requirements of in situ, fast, microscale, contactless, and nondestructive features due to their inherent limitations. Herein, SHG polarimetry is introduced to probe the multioriented polarizations on a nanosized multiaxial molecular ferroelectric, i.e., TMCM-CdCl3 nanoplates, as an example. Combined with the analysis of the second-order susceptibility tensor, SHG polarimetry could serve as an effective method to detect the polarization orders and domain distributions of molecular ferroelectrics. Profiting from the full-optical feature, SHG polarimetry can even be performed on samples covered by transparent mediums, 2D materials, or thin metal electrodes. Our research might spark further fundamental studies and expand the application boundaries of next-generation ferroelectric materials.

11.
Cancer Cell ; 41(7): 1345-1362.e9, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37352863

RESUMO

Lineage plasticity causes therapeutic resistance; however, it remains unclear how the fate conversion and phenotype switching of cancer-associated fibroblasts (CAFs) are implicated in disease relapse. Here, we show that androgen deprivation therapy (ADT)-induced SPP1+ myofibroblastic CAFs (myCAFs) are critical stromal constituents that drive the development of castration-resistant prostate cancer (CRPC). Our results reveal that SPP1+ myCAFs arise from the inflammatory CAFs in hormone-sensitive PCa; therefore, they represent two functional states of an otherwise ontogenically identical cell type. Antiandrogen treatment unleashes TGF-ß signaling, resulting in SOX4-SWI/SNF-dependent CAF phenotype switching. SPP1+ myCAFs in turn render PCa refractory to ADT via an SPP1-ERK paracrine mechanism. Importantly, these sub-myCAFs are associated with inferior therapeutic outcomes, providing the rationale for inhibiting polarization or paracrine mechanisms to circumvent castration resistance. Collectively, our results highlight that therapy-induced phenotypic switching of CAFs is coupled with disease progression and that targeting this stromal component may restrain CRPC.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Reprogramação Celular , Recidiva Local de Neoplasia/tratamento farmacológico , Castração , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição SOXC/genética
12.
Front Microbiol ; 14: 1093668, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998407

RESUMO

In this study, we isolated a lytic Pseudomonas aeruginosa phage (vB_PaeP_ASP23) from the sewage of a mink farm, characterized its complete genome and analyzed the function of its putative lysin and holin. Morphological characterization and genome annotation showed that phage ASP23 belonged to the Krylovirinae family genus Phikmvvirus, and it had a latent period of 10 min and a burst size of 140 pfu/infected cell. In minks challenged with P. aeruginosa, phage ASP23 significantly reduced bacterial counts in the liver, lung, and blood. The whole-genome sequencing showed that its genome was a 42,735-bp linear and double-stranded DNA (dsDNA), with a G + C content of 62.15%. Its genome contained 54 predicted open reading frames (ORFs), 25 of which had known functions. The lysin of phage ASP23 (LysASP), in combination with EDTA, showed high lytic activity against P. aeruginosa L64. The holin of phage ASP23 was synthesized by M13 phage display technology, to produce recombinant phages (HolASP). Though HolASP exhibited a narrow lytic spectrum, it was effective against Staphylococcus aureus and Bacillus subtilis. However, these two bacteria were insensitive to LysASP. The findings highlight the potential of phage ASP23 to be used in the development of new antibacterial agents.

13.
Cancer Lett ; 559: 216104, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-36863507

RESUMO

Hepatoid adenocarcinoma (HAC) is a rare, malignant, extrahepatic tumor with histologic features similar to those of hepatocellular carcinoma. HAC is most often associated with elevated alpha-fetoprotein (AFP). HAC can occur in multiple organs, including the stomach, esophagus, colon, pancreas, lungs, and ovaries. HAC differs greatly from typical adenocarcinoma in terms of its biological aggression, poor prognosis, and clinicopathological characteristics. However, the mechanisms underlying its development and invasive metastasis remain unclear. The purpose of this review was to summarize the clinicopathological features, molecular traits, and molecular mechanisms driving the malignant phenotype of HAC, in order to support the clinical diagnosis and treatment of HAC.


Assuntos
Adenocarcinoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/tratamento farmacológico , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas
14.
Mater Horiz ; 10(3): 869-874, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36628648

RESUMO

The electrocaloric effect (ECE) is an efficient and environmentally friendly method for solid-state refrigeration driven by an electric field. However, disregarding the ECE performance, the mass of materials also limits the amount of energy transferred in the cooling process. While molecular ECE materials have been attracting intensive attention with their excellent ECE properties, most reported molecular compounds can only be utilized in the form of thin films or single crystals. Unlike inorganic ceramics, molecular thin films and single crystals are very difficult to prepare in a large amount, which greatly restrains the future application of those materials. In this work, we report an excellent molecular ECE material in the form of polycrystalline molecular ceramics. Such molecular ceramics are composed of plastic molecular ferroelectrics, and can fulfil the requirement of large mass, easy processing, excellent performance and low energy consumption. Our molecular ceramic of HQReO4 (HQ: protonated quinuclidine) demonstrates an isothermal entropy change of 5.8 J K-1 kg-1 and an adiabatic temperature change of 3.1 K. Notably, by a simple low-temperature pressing process without added adhesives (about 373 K), an HQReO4 molecular ceramic block can be obtained, and its ECE performance is observed to be comparable to that of single crystals, for the first time. This work proposes a new application form for molecular electrocaloric materials, which opens up new ideas for solid-state refrigeration.

15.
Virus Res ; 324: 199026, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36529302

RESUMO

As an aquatic animal of great commercial relevance, Penaeus vannamei is currently the dominant species of cultured shrimp in China and many other countries worldwide. In recent years, the outbreak of glass post-larvae disease (GPD), which accounts for more than 90% of the mortality of shrimp seedlings in serious cases, in many regions of China has caused significant losses and threatened the sustainability of the aquaculture industry and the economy. It is extremely urgent to determine the infectious agent of GPD in P. vannamei. In this work, we performed metagenomic sequencing of glass post-larvae collected from diseased prawns in Tangshan Hebei, where GPD broke out recently. An evolutionary tree was constructed by MEGA 7 to understand the evolutionary history and relationship of the pathogen genome. A novel virus in the family Marnaviridae was first identified in P. vannamei suffering from GPD, and we tentatively named this virus Baishivirus (GenBank: ON550424). The identified pathogen was validated according to Koch's rule with a pathogenic challenge assay and reverse transcription-polymerase chain reaction. There was only 8% query coverage with 64.96% identity in the Baishivirus genome when compared with its most closely related genome sequence of Wenzhou picorna-like virus 21 reported in 2016. Baishivirus genomic RNA is 9.895 kb in length and encodes three potential open reading frames (ORFs). The identification of Baishivirus in P. vannamei enriches the family Marnaviridae and potentially provides a new candidate to study and prevent GPD in the aquaculture industry.


Assuntos
Penaeidae , Vírus de RNA , Animais , Genoma , Genômica , China
16.
Food Chem ; 407: 135126, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36493471

RESUMO

Effects of sweep frequency ultrasound (SFU) pretreatment of a new multifunctional ultrasonic equipment on hydrolysis characteristics of zeins and angiotensin-converting enzyme (ACE) inhibitory activity of zein hydrolysates were investigated. Degree of hydrolysis of zeins reached the highest of 25.93 % and 25.72 % at 40 kHz and 25/40 kHz, respectively. While 25/40 kHz increased solubility, surface hydrophobicity, particle size uniform of zeins and ACE inhibitory activities of the hydrolysates significantly. Endogenous fluorescence indicated that 25/40 kHz promoted unfolding of protein molecules and exposure of hydrophobic residues, thereby facilitating enzymatic hydrolysis. Circular dichroism spectrum and Fourier transform infrared spectrometer illustrated that 25/40 kHz unfolded protein molecules and decreased α-helical contents remarkably. Gel permeation chromatography showed that more small-molecule active peptides were obtained from hydrolysates at 25/40 kHz. In conclusion, SFU pretreatment at 25/40 kHz with the new equipment before proteolysis is an efficient method to improve ACE inhibitory activity of the hydrolysates.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Zeína , Inibidores da Enzima Conversora de Angiotensina/química , Zeína/metabolismo , Peptídeos/química , Hidrólise , Proteólise , Hidrolisados de Proteína/química
17.
J Cell Commun Signal ; 17(1): 89-102, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36042157

RESUMO

Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). It is also correlated to transforming growth factor-ß1 (TGF-ß1) expression, a crucial mediator in the interaction of cancer cells with TME. In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-ß expression (r = 0.7125). The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-ß1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). Collectively, our finding suggested CHPF may function as an oncogene and is highly expressed in human BRCA tissues. Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression.

18.
Molecules ; 27(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36558030

RESUMO

As one of the vital shrubs growing in crusted areas in China, Artemisia ordosica (belonging to the Asteraceae family) is abundant in essential oil, and its aerial part's essential oil has been reported to have some biological activities during the flowering and fruit set stage, and has been used in folk medicine. However, little is known about the biological activities of its aerial part's essential oil during the vegetative period. Thus, the purpose of this work was to determine the chemical composition and evaluate the antioxidant and antibacterial potencies of the essential oil extracted from A. ordosica aerial parts during the vegetative stage. Gas chromatography coupled with mass spectrometry (GC-MS) revealed that spathulenol (9.93%) and α-curcumene (9.24%), both sesquiterpenes, were the most abundant of the 74 chemical constituents detected in the essential oil of A. ordosica. The antioxidant activity of the essential oil was found to be relatively moderate against 2,2-diphenylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radical (OH●) radicals. The essential oil exhibited strong antibacterial activity against Staphylococcus aureus, Salmonella abony and Escherichia coli, with minimum inhibitory concentrations (MICs) of 2.5, 5, and 10 µL/mL, respectively. The results indicate that the essential oil of A. ordosica possesses notable antibacterial properties as well as antioxidant capability and can thus be employed as a natural ingredient which can be used as a substitute for antibiotics in the animal feed industry. However, in vivo toxicological studies are still required to determine the safety level and beneficial outcomes of the A. ordosica essential oil for future utilization.


Assuntos
Artemisia , Óleos Voláteis , Animais , Óleos Voláteis/química , Antioxidantes/química , Artemisia/química , Antibacterianos/química , Componentes Aéreos da Planta/química , Testes de Sensibilidade Microbiana
19.
Nat Commun ; 13(1): 7281, 2022 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435834

RESUMO

Chronic inflammation and an immunosuppressive microenvironment promote prostate cancer (PCa) progression and diminish the response to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here, we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation-induced IKKß activation to shape the immunosuppressive tumor microenvironment (TME). Prostate-specific deletion of Arid1a cooperates with Pten loss to accelerate prostate tumorigenesis. We identify polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) as the major infiltrating immune cell type that causes immune evasion and reveal that neutralization of PMN-MDSCs restricts the progression of Arid1a-deficient tumors. Mechanistically, inflammatory cues activate IKKß to phosphorylate ARID1A, leading to its degradation via ß-TRCP. ARID1A downregulation in turn silences the enhancer of A20 deubiquitinase, a critical negative regulator of NF-κB signaling, and thereby unleashes CXCR2 ligand-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-κB antibody or targeting CXCR2 combined with ICB for advanced PCa. Together, our findings highlight that the IKKß/ARID1A/NF-κB feedback axis integrates inflammation and immunosuppression to promote PCa progression.


Assuntos
Células Supressoras Mieloides , Neoplasias da Próstata , Masculino , Humanos , Próstata/metabolismo , Quimiotaxia , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Neoplasias da Próstata/metabolismo , NF-kappa B/metabolismo , Receptores de Interleucina-8B/metabolismo , Proteínas Serina-Treonina Quinases , Inflamação/genética , Inflamação/metabolismo , Microambiente Tumoral/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
Front Microbiol ; 13: 938616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051756

RESUMO

Salmonella enterica subspecies enterica serovar abortus equi (S. Abortus equi) is the most common cause of abortion in mares. It has recently been found to cause abortion in donkeys more frequently in China. A novel virulent bacteriophage vB_SabS_Sds2 (hereafter designated as Sds2) was isolated from the feces of donkeys using a S. Abortus equi strain as a host. Phage Sds2 had an isometric polyhedral head and an uncontracted long tail, belonging to the Tequintavirus, Markadamsvirinae, Demerecviridae, Caudovirales. The genome of phage Sds2 was 114,770 bp, with a GC content of 40.26%. The genome contained 160 open reading frames (ORFs), and no ORFs were associated with pathogenicity, drug resistance, or lysogenization by sequence analysis. Both genome annotation and phylogenetic analysis indicated that phage Sds2 was highly similar to T5-like bacteriophages. Phage Sds2 could lyse 100% (30/30) of S. Abortus equi strains, 25.3% (24/95) of other serotypes of Salmonella strains, and 27.6% (8/29) of Escherichia coli strains using the double-layer agar plate method. The in vitro test showed that phage Sds2 had high bactericidal activity against S. Abortus equi at a wide range of MOIs. The in vivo test indicated that phage Sds2 had an inhibitory effect on abortion in mice challenged with S. Abortus equi. In general, phage Sds2 is a novel lytic phage with a wide host range and has the potential to prevent abortion caused by S. Abortus equi.

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